Ctip1 Regulates the Balance between Specification of Distinct Projection Neuron Subtypes in Deep Cortical Layers.
The molecular linkage between neocortical projection neuron subtype and area development, which enables the establishment of functional areas by projection neuron populations appropriate for specific sensory and motor functions, is poorly understood. Here, we report that Ctip1 controls precision of neocortical development by regulating subtype identity in deep-layer projection neurons. Ctip1 is expressed by postmitotic callosal and corticothalamic projection neurons but is excluded over embryonic development from corticospinal motor neurons, which instead express its close relative, Ctip2. Loss of Ctip1 function results in a striking bias in favor of subcerebral projection neuron development in sensory cortex at the expense of corticothalamic and deep-layer callosal development, while misexpression of Ctip1 in vivo represses subcerebral gene expression and projections. As we report in a paired paper, Ctip1 also controls acquisition of sensory area identity. Therefore, Ctip1 couples subtype and area specification, enabling specific functional areas to organize precise ratios of appropriate output projections.
Department of Stem Cell and Regenerative Biology, Center for Brain Science and Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA; Harvard Medical School, Boston, MA 02115, USA.
Mollie B
MB
Woodworth
Department of Stem Cell and Regenerative Biology, Center for Brain Science and Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA; Harvard Medical School, Boston, MA 02115, USA.
Luciano C
LC
Greig
Department of Stem Cell and Regenerative Biology, Center for Brain Science and Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA; Harvard Medical School, Boston, MA 02115, USA.
Kevin X
KX
Liu
Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX 78712, USA.
Gregory C
GC
Ippolito
Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX 78712, USA.
Haley O
HO
Tucker
Department of Stem Cell and Regenerative Biology, Center for Brain Science and Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA; Harvard Medical School, Boston, MA 02115, USA. Electronic address: jeffrey_macklis@harvard.edu.
Jeffrey D
JD
Macklis
D000818:Animals; D000071437:Axon Guidance; D001369:Axons / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002465:Cell Movement; D002540:Cerebral Cortex / Q000166:cytology*; D005260:Female; D018398:Homeodomain Proteins / Q000378:metabolism; D019426:Integrases / Q000378:metabolism; D051379:Mice; D008938:Mitosis; D009154:Mutation / Q000235:genetics; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology; D013788:Thalamus / Q000166:cytology; D014157:Transcription Factors / Q000378:metabolism; D000099260:Empty Spiracles Homeobox Proteins
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D018398:Homeodomain Proteins; D019426:Integrases; D014157:Transcription Factors; D000099260:Empty Spiracles Homeobox Proteins; C501070:RBBP8 protein, mouse; C045073:Cre recombinase