PAX2 is expressed in multiple spinal cord interneurons, including a population of EN1+ interneurons that require PAX6 for their development.

Members of the PAX family of transcription factors are candidates for controlling cell identity in the spinal cord. We have morphologically analyzed cells that express one of these transcription factors, PAX2, demonstrating multiple interneuron cell types express PAX2. Two ventral populations of PAX2-expressing interneurons in the spinal cord are marked by coexpression of the transcription factors, EN1 and EVX1. Interestingly, the expression domains of PAX2, EN1 and EVX1 in postmitotic neurons correlate closely with those of Pax6 and Pax7 in the ventricular zone, implicating these patterning genes in the regulation of PAX2, EN1 and EVX1. We show that one of these patterning genes, Pax6, is required for the correct specification of ventral PAX2+ interneurons that coexpress EN1. These results demonstrate that the early activity of patterning genes in the ventricular zone determines interneuron identity in the spinal cord.

[1]  B. Rexed.  The cytoarchitectonic organization of the spinal cord in the cat , 1952, The Journal of comparative neurology.

[2]  E. Jankowska,et al.  Morphology of interneurones mediating Ia reciprocal inhibition of motoneurones in the spinal cord of the cat , 1972, The Journal of physiology.

[3]  M. Hollyday.  Organization of motor pools in the chick lumbar lateral motor column , 1980, The Journal of comparative neurology.

[4]  J. Clarke,et al.  Activity of commissural interneurons in spinal cord of Xenopus embryos. , 1984, Journal of neurophysiology.

[5]  G K Lewis,et al.  Isolation of monoclonal antibodies specific for human c-myc proto-oncogene product , 1985, Molecular and cellular biology.

[6]  A. Roberts,et al.  The early development of neurons with GABA immunoreactivity in the CNS of Xenopus laevis embryos , 1987, The Journal of comparative neurology.

[7]  J. Silver,et al.  Growth pattern of pioneering chick spinal cord axons. , 1987, Developmental biology.

[8]  R. Oppenheim,et al.  Onset and development of intersegmental projections in the chick embryo spinal cord , 1988, The Journal of comparative neurology.

[9]  C. Goodman,et al.  Control of neuronal fate by the Drosophila segmentation gene even-skipped , 1988, Nature.

[10]  A. Roberts,et al.  Development and characterization of commissural interneurones in the spinal cord of Xenopus laevis embryos revealed by antibodies to glycine. , 1988, Development.

[11]  A. Frankfurter,et al.  Development of the peripheral trigeminal system in the chick revealed by an isotype‐specific anti‐beta‐tubulin monoclonal antibody , 1989, The Journal of comparative neurology.

[12]  E. Knapik,et al.  Spatially and temporally restricted expression of Pax2 during murine neurogenesis. , 1990, Development.

[13]  P. Gruss,et al.  The murine paired box gene, Pax7, is expressed specifically during the development of the nervous and muscular system , 1990, Mechanisms of Development.

[14]  P. Gruss,et al.  A murine even‐skipped homologue, Evx 1, is expressed during early embryogenesis and neurogenesis in a biphasic manner. , 1990, The EMBO journal.

[15]  G. Saunders,et al.  Mouse Small eye results from mutations in a paired-like homeobox-containing gene , 1991, Nature.

[16]  A. Lumsden.  Motorizing the spinal cord , 1991, Cell.

[17]  A. Joyner,et al.  Examining pattern formation in mouse, chicken and frog embryos with an En-specific antiserum. , 1991, Development.

[18]  T. Jessell,et al.  Control of cell pattern in the developing nervous system: Polarizing activity of the floor plate and notochord , 1991, Cell.

[19]  G. Dressler,et al.  Pax-2 is a DNA-binding protein expressed in embryonic kidney and Wilms tumor. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[20]  A. Joyner,et al.  Cloning and sequence comparison of the mouse, human, and chicken engrailed genes reveal potential functional domains and regulatory regions. , 1992, Developmental genetics.

[21]  M. Westerfield,et al.  Comparative analysis of Pax-2 protein distributions during neurulation in mice and zebrafish , 1992, Mechanisms of Development.

[22]  Peter Gruss,et al.  Pax in development , 1992, Cell.

[23]  T. Jessell,et al.  Early stages of motor neuron differentiation revealed by expression of homeobox gene Islet-1. , 1992, Science.

[24]  V. Hamburger,et al.  A series of normal stages in the development of the chick embryo. 1951. , 2012, Developmental dynamics : an official publication of the American Association of Anatomists.

[25]  P. Raymond,et al.  Regeneration of dopaminergic neurons in goldfish retina. , 1992, Development.

[26]  W D Snider,et al.  Development of commissural neurons in the embryonic rat spinal cord , 1992, The Journal of comparative neurology.

[27]  S. Ben‐Sasson,et al.  Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation , 1992, The Journal of cell biology.

[28]  M. Dush,et al.  Analysis of mouse Evx genes: Evx-1 displays graded expression in the primitive streak. , 1992, Developmental biology.

[29]  R. Miller,et al.  Oligodendrocyte precursors originate at the ventral ventricular zone dorsal to the ventral midline region in the embryonic rat spinal cord. , 1993, Development.

[30]  T. Jessell,et al.  Control of cell pattern in the neural tube: Motor neuron induction by diffusible factors from notochord and floor plate , 1993, Cell.

[31]  W. Richardson,et al.  A singularity of PDGF alpha-receptor expression in the dorsoventral axis of the neural tube may define the origin of the oligodendrocyte lineage. , 1993, Development.

[32]  W D Snider,et al.  Development of interneurons with ipsilateral projections in embryonic rat spinal cord , 1994, The Journal of comparative neurology.

[33]  T. Jessell,et al.  Topographic organization of embryonic motor neurons defined by expression of LIM homeobox genes , 1994, Cell.

[34]  N. Patel,et al.  engrailed controls glial/neuronal cell fate decisions at the midline of the central nervous system , 1994, Neuron.

[35]  D. Kooy,et al.  Developmental expression of a novel murine homeobox gene (Chx10): Evidence for roles in determination of the neuroretina and inner nuclear layer , 1994, Neuron.

[36]  A. Joyner,et al.  Multiple developmental defects in Engrailed-1 mutant mice: an early mid-hindbrain deletion and patterning defects in forelimbs and sternum. , 1994, Development.

[37]  T. Jessell,et al.  Floor plate and motor neuron induction by vhh-1, a vertebrate homolog of hedgehog expressed by the notochord , 1994, Cell.

[38]  M. Goulding,et al.  Regulation of Pax-3 expression in the dermomyotome and its role in muscle development. , 1994, Development.

[39]  M. Capecchi,et al.  Targeted disruption of the even-skipped gene, evx1, causes early postimplantation lethality of the mouse conceptus. , 1994, Genes & development.

[40]  J. Sanes,et al.  Migratory paths of neurons and glia in the embryonic chick spinal cord , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[41]  P. Gruss,et al.  Pax-2 controls multiple steps of urogenital development. , 1995, Development.

[42]  T. Jessell,et al.  Dorsal differentiation of neural plate cells induced by BMP-mediated signals from epidermal ectoderm , 1995, Cell.

[43]  M. Dickinson,et al.  Dorsalization of the neural tube by the non-neural ectoderm. , 1995, Development.

[44]  S. Carroll,et al.  Specification of neuroblast identity in the Drosophila embryonic central nervous system by gooseberry-distal , 1995, Nature.

[45]  Johan Ericson,et al.  Two Critical Periods of Sonic Hedgehog Signaling Required for the Specification of Motor Neuron Identity , 1996, Cell.

[46]  T. Jessell,et al.  Diversity and Pattern in the Developing Spinal Cord , 1996, Science.

[47]  T. Jessell,et al.  Requirement for LIM Homeobox Gene Isl1 in Motor Neuron Generation Reveals a Motor Neuron– Dependent Step in Interneuron Differentiation , 1996, Cell.

[48]  Randall R. Reed,et al.  Role of Olf-1 and Pax-6 Transcription Factors in Neurodevelopment , 1996, The Journal of Neuroscience.

[49]  R. Guillery.  Histology of the Nervous System by Santiago Ramón y Cajal. Translated into English from the French edition by Neely Swanson and Larry W. Swanson, Oxford University Press, 1995. $195.00 (1672 pp) ISBN 0 19 507 4017 , 1996, Trends in Neurosciences.

[50]  P. Beachy,et al.  Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function , 1996, Nature.

[51]  C. Doe,et al.  Neurogenesis in the insect central nervous system , 1996, Current Opinion in Neurobiology.

[52]  M. Goulding,et al.  Regulation of vertebrate neural cell fate by transcription factors , 1996, Current Opinion in Neurobiology.

[53]  B. Morgan,et al.  Manipulating gene expression with replication-competent retroviruses. , 1996, Methods in cell biology.

[54]  T. Jessell,et al.  Pax6 Controls Progenitor Cell Identity and Neuronal Fate in Response to Graded Shh Signaling , 1997, Cell.

[55]  M. Nakafuku,et al.  Pax-6 is involved in the specification of hindbrain motor neuron subtype. , 1997, Development.