A switch in numb isoforms is a critical step in cortical development
| Autor: | Stephen Bellum, Jennifer A. Rochira, George N. Nikopoulos, Joseph M. Verdi, Mahmud Bani-Yaghoub, Chris J. Kubu, Rebecca A. Cowling |
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| Rok vydání: | 2007 |
| Předmět: |
Gene isoform
animal structures Morpholino Blotting Western Notch signaling pathway Embryonic Development Nerve Tissue Proteins Biology Mice Basic Helix-Loop-Helix Transcription Factors Animals Protein Isoforms Progenitor cell Cells Cultured Progenitor Neurons Receptors Notch Reverse Transcriptase Polymerase Chain Reaction fungi Neurogenesis Gene Expression Regulation Developmental Membrane Proteins Cell Differentiation Anatomy Oligonucleotides Antisense Immunohistochemistry Cell biology embryonic structures NUMB Neural development hormones hormone substitutes and hormone antagonists Developmental Biology |
| Zdroj: | Developmental dynamics : an official publication of the American Association of Anatomists. 236(3) |
| ISSN: | 1058-8388 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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