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A switch in numb isoforms is a critical step in cortical development
Author(s) -
BaniYaghoub Mahmud,
Kubu Chris J.,
Cowling Rebecca,
Rochira Jennifer,
Nikopoulos George N.,
Bellum Stephen,
Verdi Joseph M.
Publication year - 2007
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.21072
Subject(s) - numb , notch signaling pathway , biology , neural stem cell , progenitor cell , microbiology and biotechnology , gene isoform , neurogenesis , cellular differentiation , signal transduction , stem cell , genetics , gene
Loss of numb function suggests that numb maintains progenitors in an undifferentiated state. Herein, we demonstrate that numb1 and numb3 are expressed in undifferentiated cortical progenitors, whereas numb2 and numb4 become prominent throughout differentiation. To further assess the role of different numb isoforms in cortical neural development, we first created a Numb‐null state with antisense morpholino, followed by the re‐expression of specific numb isoforms. The re‐expression of numb1 or numb3 resulted in a significant reduction of neural differentiation, correlating with an expansion of the cortical progenitor pool. In contrast, the expression of numb2 or numb4 resulted in a reduction of proliferating progenitors and a corresponding increase in mammalian achete‐scute homologue (MASH1) expression, concurrent with the appearance of the mitogen‐activated protein‐2–positive neurons. Of interest, the effect of numb isoforms on neural differentiation could not be directly related to Notch, because classic canonical Notch signaling assays failed to uncover any differences in the four isoforms to inhibit the Notch downstream events. This finding suggests that numb may have other signaling properties during neuronal differentiation in addition to augmenting notch signal strength. Developmental Dynamics 236:696–705, 2007. © 2007 Wiley‐Liss, Inc.