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First published online 6 October 2004
doi: 10.1242/dev.01430

Development 131, 5441-5448 (2004)
Published by The Company of Biologists 2004
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Id4 regulates neural progenitor proliferation and differentiation in vivo

Kyuson Yun1,2,*, Akio Mantani1,*,{dagger}, Sonia Garel2, John Rubenstein2 and Mark A. Israel1,{ddagger}

1 Department of Pediatrics and Genetics and the Norris Cotton Cancer Center, Dartmouth Medical School, Dartmouth-Hitchcock Medical Center, 1 Medical Center Drive, Lebanon, NH 03756, USA
2 Nina Ireland Laboratory of Developmental Neurobiology, Department of Psychiatry, LPPI, University of California, 401 Parnassus, Box 0984, San Francisco, CA 94143-0984, USA

{ddagger} Author for correspondence (e-mail: mark.a.israel{at}dartmouth.edu)

Accepted 2 September 2004

The mechanisms that determine whether a precursor cell re-enters the cell cycle or exits and differentiates are crucial in determining the types and numbers of cells that constitute a particular organ. Here, we report that Id4 is required for normal brain size, and regulates lateral expansion of the proliferative zone in the developing cortex and hippocampus. In its absence, proliferation of stem cells in the ventricular zone (VZ) is compromised. In early cortical progenitors, Id4 is required for the normal G1-S transition. By contrast, at later ages, ectopically positioned proliferating cells are found in the mantle zone of the Id4-/- cortex. These observations, together with evidence for the premature differentiation of early cortical stem cells, indicate that Id4 has a unique and complex function in regulating neural stem cell proliferation and differentiation.

Key words: Id4, Id2, Cortex, Hippocampus, G1-S, Cell cycle, Neurogenesis, CNS development


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