Novitch, Bennett

Professor, Neurobiology

Member, Brain Research Institute

CTSI

Cell & Developmental Biology GPB Home Area

Eli & Edythe Broad Center of Regenerative Medicine & Stem Cell Research

Gene Regulation GPB Home Area

JCCC Cancer and Stem Cell Biology Program Area

Neuroscience GPB Home Area

Biography

The main goals of the Novitch laboratory are to determine the molecular pathways that direct the differentiation of neural stem and progenitor cells, and assembly of neural circuits. Most of their work focuses on the growth factor signals, transcriptional networks, and downstream effectors that control the formation of specific classes of neurons and glial cells in the developing brain and spinal cord. Insights into these fundamental mechanisms are essential for determining the function of stem and progenitor cells in both normal development and diseased states, and for developing methods to manipulate stem and progenitor cells to direct the generation of specific types of neurons and glial cells and facilitate the repair of damaged neural tissue. Projects within the laboratory span multiple areas including molecular and cellular biology, transcriptional regulation, cellular differentiation, stem cell biology, and neural development. Much of the Novitch lab's recent work has focused on applying our understanding of neural development to direct the formation of spinal cord and brain tissues from human embryonic and induced pluripotent stem cells using both two-dimensional culture methods and recently developed three-dimensional organoid approaches. These technologies offer an unprecedented opportunity to investigate biological features of human development and pathologies that cannot be easily modeling in conventional model organisms such as mice. The lab seeks to apply these technologies towards modeling the formation and function of neural circuits and investigating the underlying causes of neurodevelopmental and neurological disorders as well as neurodegenerative diseases.  

Pearson CA, Moore DM, Tucker HO, Hu H, Miquelajáuregui A, Novitch BG   Foxp1 controls neural stem cell competence and bias towards deep layer cortical fate Cell Reports, 2020; .

Watanabe M, Haney JR, Vishlaghi N, Turcios F, Buth JE, Gu W, Collier AJ, Miranda OA, Chen D, Sabri S, Clark AT, Plath K, Christofk HR, Gandal MJ, Novitch BG   TGFβ superfamily signaling regulates the state of human stem cell pluripotency and competency to create telencephalic organoids bioRxiv, 2019; 875773.

Samarasinghe RA, Miranda OA, Mitchell S, Ferando I, Watanabe M, Buth JE, Kurdian A, Golshani P, Plath K, Lowry WE, Parent JM, Mody I, Novitch BG   Identification of neural oscillations and epileptiform changes in human brain organoids bioRxiv, 2019; 820183.

Andrews Madeline G, Kong Jennifer, Novitch Bennett G, Butler Samantha J   New perspectives on the mechanisms establishing the dorsal-ventral axis of the spinal cord Current topics in developmental biology, 2019; 132: 417-450.

Han Albert Y, Gupta Sandeep, Novitch Bennett G   Molecular specification of facial branchial motor neurons in vertebrates Developmental biology, 2018; 16(2): e2003127.

Sagner Andreas, Gaber Zachary B, Delile Julien, Kong Jennifer H, Rousso David L, Pearson Caroline A, Weicksel Steven E, Melchionda Manuela, Mousavy Gharavy S Neda, Briscoe James, Novitch Bennett G   Olig2 and Hes regulatory dynamics during motor neuron differentiation revealed by single cell transcriptomics PLoS biology, 2018; 16(2): e2003127.

Li Chunfeng, Deng Yong-Qiang, Wang Shuo, Ma Feng, Aliyari Roghiyh, Huang Xing-Yao, Zhang Na-Na, Watanabe Momoko, Dong Hao-Long, Liu Ping, Li Xiao-Feng, Ye Qing, Tian Min, Hong Shuai, Fan Junwan, Zhao Hui, Li Lili, Vishlaghi Neda, Buth Jessie E, Au Connie, Liu Ying, Lu Ning, Du Peishuang, Qin F Xiao-Feng, Zhang Bo, Gong Danyang, Dai Xinghong, Sun Ren, Novitch Bennett G, Xu Zhiheng, Qin Cheng-Feng, Cheng Genhong   25-Hydroxycholesterol Protects Host against Zika Virus Infection and Its Associated Microcephaly in a Mouse Model Immunity, 2017; 46(3): 446-456.

Sangwan Smriti, Zhao Anni, Adams Katrina L, Jayson Christina K, Sawaya Michael R, Guenther Elizabeth L, Pan Albert C, Ngo Jennifer, Moore Destaye M, Soriaga Angela B, Do Thanh D, Goldschmidt Lukasz, Nelson Rebecca, Bowers Michael T, Koehler Carla M, Shaw David E, Novitch Bennett G, Eisenberg David S   Atomic structure of a toxic, oligomeric segment of SOD1 linked to amyotrophic lateral sclerosis (ALS) Proceedings of the National Academy of Sciences of the United States of America, 2017; 114(33): 8770-8775.

Huang Chengyang, Su Trent, Xue Yong, Cheng Chen, Lay Fides D, McKee Robin A, Li Meiyang, Vashisht Ajay, Wohlschlegel James, Novitch Bennett G, Plath Kathrin, Kurdistani Siavash K, Carey Michael   Cbx3 maintains lineage specificity during neural differentiation Genes Dev, 2017; 31(3): 241-246.

Varadarajan Supraja G, Kong Jennifer H, Phan Keith D, Kao Tzu-Jen, Panaitof S Carmen, Cardin Julie, Eltzschig Holger, Kania Artur, Novitch Bennett G, Butler Samantha J   Netrin1 Produced by Neural Progenitors, Not Floor Plate Cells, Is Required for Axon Guidance in the Spinal Cord Neuron, 2017; .

Watanabe Momoko, Buth Jessie E, Vishlaghi Neda, de la Torre-Ubieta Luis, Taxidis Jiannis, Khakh Baljit S, Coppola Giovanni, Pearson Caroline A, Yamauchi Ken, Gong Danyang, Dai Xinghong, Damoiseaux Robert, Aliyari Roghiyh, Liebscher Simone, Schenke-Layland Katja, Caneda Christine, Huang Eric J, Zhang Ye, Cheng Genhong, Geschwind Daniel H, Golshani Peyman, Sun Ren, Novitch Bennett G   Self-Organized Cerebral Organoids with Human-Specific Features Predict Effective Drugs to Combat Zika Virus Infection Cell reports, 2017; 21(2): 517-532.

Adams Katrina L, Rousso David L, Umbach Joy A, Novitch Bennett G   Foxp1-mediated programming of limb-innervating motor neurons from mouse and human embryonic stem cells Nat Commun, 2015; 6: 6778.

Kong Jennifer H, Yang Linlin, Dessaud Eric, Chuang Katherine, Moore Destaye M, Rohatgi Rajat, Briscoe James, Novitch Bennett G   Notch Activity Modulates the Responsiveness of Neural Progenitors to Sonic Hedgehog Signaling Dev Cell, 2015; 33(4): 373-87.

Linares Anthony J, Lin Chia-Ho, Damianov Andrey, Adams Katrina L, Novitch Bennett G, Black Douglas L   The splicing regulator PTBP1 controls the activity of the transcription factor Pbx1 during neuronal differentiation eLife, 2015; 4: e09268.

Niewiadomski Pawel, Kong Jennifer H, Ahrends Robert, Ma Yan, Humke Eric W, Khan Sohini, Teruel Mary N, Novitch Bennett G, Rohatgi Rajat   Gli protein activity is controlled by multisite phosphorylation in vertebrate hedgehog signaling Cell Rep, 2014; 6(1): 168-81.

Pearson Caroline A, Butler Samantha J, Novitch Bennett G   Neuronal organization: unsticking the cadherin code Curr Biol, 2014; 24(23): R1127-9.

Xu Ben, Hrycaj Steven M, McIntyre Daniel C, Baker Nicholas C, Takeuchi Jun K, Jeannotte Lucie, Gaber Zachary B, Novitch Bennett G, Wellik Deneen M   Hox5 interacts with Plzf to restrict Shh expression in the developing forelimb Proc Natl Acad Sci USA, 2013; 110(48): 19438-43.

Kong Jennifer H, Butler Samantha J, Novitch Bennett G   My brain told me to do it Dev Cell, 2013; 25(5): 436-8.

Gaber Zachary B, Butler Samantha J, Novitch Bennett G   PLZF regulates fibroblast growth factor responsiveness and maintenance of neural progenitors PLoS Biol, 2013; 11(10): e1001676.

Jacob John, Kong Jennifer, Moore Steven, Milton Christopher, Sasai Noriaki, Gonzalez-Quevedo Rosa, Terriente Javier, Imayoshi Itaru, Kageyama Ryoichiro, Kageyama Ryoichoro, Wilkinson David G, Novitch Bennett G, Briscoe James   Retinoid acid specifies neuronal identity through graded expression of Ascl1 Curr Biol, 2013; 23(5): 412-8.

Wang Yuan, Kim Edward, Wang Xiaojing, Novitch Bennett G, Yoshikawa Kazuaki, Chang Long-Sheng, Zhu Yuan   ERK inhibition rescues defects in fate specification of Nf1-deficient neural progenitors and brain abnormalities Cell, 2012; 150(4): 816-30.

Rousso David L, Pearson Caroline Alayne, Gaber Zachary B, Miquelajauregui Amaya, Li Shanru, Portera-Cailliau Carlos, Morrisey Edward E, Novitch Bennett G   Foxp-mediated suppression of N-cadherin regulates neuroepithelial character and progenitor maintenance in the CNS Neuron, 2012; 74(2): 314-30.

Umbach Joy A, Adams Katrina L, Gundersen Cameron B, Novitch Bennett G   Functional neuromuscular junctions formed by embryonic stem cell-derived motor neurons PLoS One, 2012; 7(5): e36049.

Roy Agnes, Francius Cedric, Rousso David L, Seuntjens Eve, Debruyn Joke, Luxenhofer Georg, Huber Andrea B, Huylebroeck Danny, Novitch Bennett G, Clotman Frederic   Onecut transcription factors act upstream of Isl1 to regulate spinal motoneuron diversification Development, 2012; 139(17): 3109-19.

Kang Peng, Lee Hyun Kyoung, Glasgow Stacey M, Finley Meggie, Donti Tataka, Gaber Zachary B, Graham Brett H, Foster Aaron E, Novitch Bennett G, Gronostajski Richard M, Deneen Benjamin   Sox9 and NFIA coordinate a transcriptional regulatory cascade during the initiation of gliogenesis Neuron, 2012; 74(1): 79-94.

Gaber Zachary B, Novitch Bennett G   All the embryo's a stage, and Olig2 in its time plays many parts Neuron, 2011; 69(5): 833-5.

Huettl Rosa-Eva, Soellner Heidi, Bianchi Elisa, Novitch Bennett G, Huber Andrea B   Npn-1 contributes to axon-axon interactions that differentially control sensory and motor innervation of the limb PLoS Biol, 2011; 9(2): e1001020.

Skaggs Kaia, Martin Donna M, Novitch Bennett G   Regulation of spinal interneuron development by the Olig-related protein Bhlhb5 and Notch signaling Development, 2011; 138(15): 3199-211.

Ribes Vanessa, Balaskas Nikolaos, Sasai Noriaki, Cruz Catarina, Dessaud Eric, Cayuso Jordi, Tozer Samuel, Yang Lin Lin, Novitch Ben, Marti Elisa, Briscoe James   Distinct Sonic Hedgehog signaling dynamics specify floor plate and ventral neuronal progenitors in the vertebrate neural tube Genes Dev, 2010; 24(11): 1186-200.

Dessaud Eric, Ribes Vanessa, Balaskas Nikolaos, Yang Lin Lin, Pierani Alessandra, Kicheva Anna, Novitch Bennett G, Briscoe James, Sasai Noriaki   Dynamic assignment and maintenance of positional identity in the ventral neural tube by the morphogen sonic hedgehog PLoS Biol, 2010; 8(6): e1000382.

Palmesino Elena, Rousso David L, Kao Tzu-Jen, Klar Avihu, Laufer Ed, Uemura Osamu, Okamoto Hitoshi, Novitch Bennett G, Kania Artur   Foxp1 and lhx1 coordinate motor neuron migration with axon trajectory choice by gating Reelin signalling PLoS Biol, 2010; 8(8): e1000446.

Karumbayaram Saravanan, Novitch Bennett G, Patterson Michaela, Umbach Joy A, Richter Laura, Lindgren Anne, Conway Anne E, Clark Amander T, Goldman Steve A, Plath Kathrin, Wiedau-Pazos Martina, Kornblum Harley I, Lowry William E   Directed differentiation of human-induced pluripotent stem cells generates active motor neurons Stem Cells, 2009; 27(4): 806-11.

Novitch Bennett G, Butler Samantha J   Reducing the mystery of neuronal differentiation Cell, 2009; 138(6): 1062-4.

Vue Tou Yia, Bluske Krista, Alishahi Amin, Yang Lin Lin, Koyano-Nakagawa Naoko, Novitch Bennett, Nakagawa Yasushi   Sonic hedgehog signaling controls thalamic progenitor identity and nuclei specification in mice J Neurosci, 2009; 29(14): 4484-97.

Rousso David L, Gaber Zachary B, Wellik Deneen, Morrisey Edward E, Novitch Bennett G   Coordinated actions of the forkhead protein Foxp1 and Hox proteins in the columnar organization of spinal motor neurons Neuron, 2008; 59(2): 226-40.

Briscoe James, Novitch Bennett G   Regulatory pathways linking progenitor patterning, cell fates and neurogenesis in the ventral neural tube Phil Trans Royal Soc B, 2008; 363(1489): 57-70.

Dessaud Eric, Yang Lin Lin, Hill Katy, Cox Barny, Ulloa Fausto, Ribeiro Ana, Mynett Anita, Novitch Bennett G, Briscoe James   Interpretation of the sonic hedgehog morphogen gradient by a temporal adaptation mechanism Nature, 2007; 450(7170): 717-20.

Mukouyama Yoh-suke, Deneen Benjamin, Lukaszewicz Agnès, Novitch Bennett G, Wichterle Hynek, Jessell Thomas M, Anderson David J   Olig2+ neuroepithelial motoneuron progenitors are not multipotent stem cells in vivo Proc Natl Acad Sci USA, 2006; 103(5): 1551-6.

Marshall Christine A G, Novitch Bennett G, Goldman James E   Olig2 directs astrocyte and oligodendrocyte formation in postnatal subventricular zone cells J Neurosci, 2005; 25(32): 7289-98.

Novitch Bennett G, Wichterle Hynek, Jessell Thomas M, Sockanathan Shanthini   A requirement for retinoic acid-mediated transcriptional activation in ventral neural patterning and motor neuron specification Neuron, 2003; 40(1): 81-95.

Qu Jian, Li Xiaofan, Novitch Bennet G, Zheng Ye, Kohn Matthew, Xie Jian-Ming, Kozinn Spencer, Bronson Roderick, Beg Amer A, Minden Audrey   PAK4 kinase is essential for embryonic viability and for proper neuronal development Mol Cell Biol, 2003; 23(20): 7122-33.

Bylund Magdalena, Andersson Elisabeth, Novitch Bennett G, Muhr Jonas   Vertebrate neurogenesis is counteracted by Sox1-3 activity Nature Neurosci, 2003; 6(11): 1162-8.

Novitch B G, Chen A I, Jessell T M   Coordinate regulation of motor neuron subtype identity and pan-neuronal properties by the bHLH repressor Olig2 Neuron, 2001; 31(5): 773-89.

Novitch B G, Spicer D B, Kim P S, Cheung W L, Lassar A B   pRb is required for MEF2-dependent gene expression as well as cell-cycle arrest during skeletal muscle differentiation Curr Biol, 1999; 9(9): 449-59.

Sellers W R, Novitch B G, Miyake S, Heith A, Otterson G A, Kaye F J, Lassar A B, Kaelin W G   Stable binding to E2F is not required for the retinoblastoma protein to activate transcription, promote differentiation, and suppress tumor cell growth Genes Dev, 1998; 12(1): 95-106.

Skapek S X, Rhee J, Kim P S, Novitch B G, Lassar A B   Cyclin-mediated inhibition of muscle gene expression via a mechanism that is independent of pRB hyperphosphorylation Mol Cell Biol, 1996; 16(12): 7043-53.

Novitch B G, Mulligan G J, Jacks T, Lassar A B   Skeletal muscle cells lacking the retinoblastoma protein display defects in muscle gene expression and accumulate in S and G2 phases of the cell cycle J Cell Biol, 1996; 135(2): 441-56.

Halevy O, Novitch B G, Spicer D B, Skapek S X, Rhee J, Hannon G J, Beach D, Lassar A B   Correlation of terminal cell cycle arrest of skeletal muscle with induction of p21 by MyoD Science, 1995; 267(5200): 1018-21.

Lassar A B, Skapek S X, Novitch B   Regulatory mechanisms that coordinate skeletal muscle differentiation and cell cycle withdrawal Curr Opin Cell Biol, 1994; 6(6): 788-94.