Involvement of numb in vertebrate retinal development: Evidence for multiple roles of numb in neural differentiation and maturation

Constance M. Dooley, Jackson James, C. Jane McGlade, Iqbal Ahmad

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Cell fate specification is regulated in part by lateral inhibition mediated by Notch signaling. Notch signaling is negatively regulated by Numb, an intrinsic factor that regulates cellular competence. In this study we have examined the involvement of Numb in retinal development, which has been shown to be influenced by Notch signaling. In the developing retina, Numb is asymmetrically distributed towards the ventricular and vitreal poles of different cells. Asymmetric localization is evident not only in mitotic cells but in postmitotic ganglion cells as well, suggesting that the subcellular distribution of Numb may play a role after cells have exited the cell cycle. This is supported by the expression of Numb in terminally differentiated neurons in the adult retina. Although Numb is an intrinsic factor, it is observed that its subcellular distribution is influenced by epigenetic cues such that a higher proportion of cells cultured at high density express Numb asymmetrically. A correlation is observed between asymmetric localization and cellular competence; cells in which Numb is asymmetric differentiate more readily in culture than those that express Numb symmetrically. We have identified alternative splice variants in the developing and adult retina that correspond to isoforms that have been shown to regulate proliferation and differentiation. The dynamic temporal expression patterns of alternative splice variants and isoforms suggest that Numb may influence proliferation and differentiation of retinal progenitors during neurogenesis and maturation of postmitotic neurons. Together, these results demonstrate the complex role of the distribution of Numb within progenitors and post-mitotic neurons.

Original languageEnglish (US)
Pages (from-to)313-325
Number of pages13
JournalJournal of Neurobiology
Volume54
Issue number2
DOIs
StatePublished - Feb 2 2003

Fingerprint

Vertebrates
Retina
Intrinsic Factor
Neurons
Mental Competency
Protein Isoforms
Neurogenesis
Epigenomics
Ganglia
Cues
Cultured Cells
Cell Cycle

Keywords

  • Asymmetric
  • Development
  • Neurogenesis
  • Notch
  • Numb
  • Progenitors
  • Retina

ASJC Scopus subject areas

  • Neuroscience(all)
  • Cellular and Molecular Neuroscience

Cite this

Involvement of numb in vertebrate retinal development : Evidence for multiple roles of numb in neural differentiation and maturation. / Dooley, Constance M.; James, Jackson; McGlade, C. Jane; Ahmad, Iqbal.

In: Journal of Neurobiology, Vol. 54, No. 2, 02.02.2003, p. 313-325.

Research output: Contribution to journalArticle

@article{ce8fbc53a8a349a587134d8b1527c7e3,
title = "Involvement of numb in vertebrate retinal development: Evidence for multiple roles of numb in neural differentiation and maturation",
abstract = "Cell fate specification is regulated in part by lateral inhibition mediated by Notch signaling. Notch signaling is negatively regulated by Numb, an intrinsic factor that regulates cellular competence. In this study we have examined the involvement of Numb in retinal development, which has been shown to be influenced by Notch signaling. In the developing retina, Numb is asymmetrically distributed towards the ventricular and vitreal poles of different cells. Asymmetric localization is evident not only in mitotic cells but in postmitotic ganglion cells as well, suggesting that the subcellular distribution of Numb may play a role after cells have exited the cell cycle. This is supported by the expression of Numb in terminally differentiated neurons in the adult retina. Although Numb is an intrinsic factor, it is observed that its subcellular distribution is influenced by epigenetic cues such that a higher proportion of cells cultured at high density express Numb asymmetrically. A correlation is observed between asymmetric localization and cellular competence; cells in which Numb is asymmetric differentiate more readily in culture than those that express Numb symmetrically. We have identified alternative splice variants in the developing and adult retina that correspond to isoforms that have been shown to regulate proliferation and differentiation. The dynamic temporal expression patterns of alternative splice variants and isoforms suggest that Numb may influence proliferation and differentiation of retinal progenitors during neurogenesis and maturation of postmitotic neurons. Together, these results demonstrate the complex role of the distribution of Numb within progenitors and post-mitotic neurons.",
keywords = "Asymmetric, Development, Neurogenesis, Notch, Numb, Progenitors, Retina",
author = "Dooley, {Constance M.} and Jackson James and McGlade, {C. Jane} and Iqbal Ahmad",
year = "2003",
month = "2",
day = "2",
doi = "10.1002/neu.10176",
language = "English (US)",
volume = "54",
pages = "313--325",
journal = "Developmental Neurobiology",
issn = "1932-8451",
publisher = "John Wiley and Sons Inc.",
number = "2",

}

TY - JOUR

T1 - Involvement of numb in vertebrate retinal development

T2 - Evidence for multiple roles of numb in neural differentiation and maturation

AU - Dooley, Constance M.

AU - James, Jackson

AU - McGlade, C. Jane

AU - Ahmad, Iqbal

PY - 2003/2/2

Y1 - 2003/2/2

N2 - Cell fate specification is regulated in part by lateral inhibition mediated by Notch signaling. Notch signaling is negatively regulated by Numb, an intrinsic factor that regulates cellular competence. In this study we have examined the involvement of Numb in retinal development, which has been shown to be influenced by Notch signaling. In the developing retina, Numb is asymmetrically distributed towards the ventricular and vitreal poles of different cells. Asymmetric localization is evident not only in mitotic cells but in postmitotic ganglion cells as well, suggesting that the subcellular distribution of Numb may play a role after cells have exited the cell cycle. This is supported by the expression of Numb in terminally differentiated neurons in the adult retina. Although Numb is an intrinsic factor, it is observed that its subcellular distribution is influenced by epigenetic cues such that a higher proportion of cells cultured at high density express Numb asymmetrically. A correlation is observed between asymmetric localization and cellular competence; cells in which Numb is asymmetric differentiate more readily in culture than those that express Numb symmetrically. We have identified alternative splice variants in the developing and adult retina that correspond to isoforms that have been shown to regulate proliferation and differentiation. The dynamic temporal expression patterns of alternative splice variants and isoforms suggest that Numb may influence proliferation and differentiation of retinal progenitors during neurogenesis and maturation of postmitotic neurons. Together, these results demonstrate the complex role of the distribution of Numb within progenitors and post-mitotic neurons.

AB - Cell fate specification is regulated in part by lateral inhibition mediated by Notch signaling. Notch signaling is negatively regulated by Numb, an intrinsic factor that regulates cellular competence. In this study we have examined the involvement of Numb in retinal development, which has been shown to be influenced by Notch signaling. In the developing retina, Numb is asymmetrically distributed towards the ventricular and vitreal poles of different cells. Asymmetric localization is evident not only in mitotic cells but in postmitotic ganglion cells as well, suggesting that the subcellular distribution of Numb may play a role after cells have exited the cell cycle. This is supported by the expression of Numb in terminally differentiated neurons in the adult retina. Although Numb is an intrinsic factor, it is observed that its subcellular distribution is influenced by epigenetic cues such that a higher proportion of cells cultured at high density express Numb asymmetrically. A correlation is observed between asymmetric localization and cellular competence; cells in which Numb is asymmetric differentiate more readily in culture than those that express Numb symmetrically. We have identified alternative splice variants in the developing and adult retina that correspond to isoforms that have been shown to regulate proliferation and differentiation. The dynamic temporal expression patterns of alternative splice variants and isoforms suggest that Numb may influence proliferation and differentiation of retinal progenitors during neurogenesis and maturation of postmitotic neurons. Together, these results demonstrate the complex role of the distribution of Numb within progenitors and post-mitotic neurons.

KW - Asymmetric

KW - Development

KW - Neurogenesis

KW - Notch

KW - Numb

KW - Progenitors

KW - Retina

UR - http://www.scopus.com/inward/record.url?scp=0037413906&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037413906&partnerID=8YFLogxK

U2 - 10.1002/neu.10176

DO - 10.1002/neu.10176

M3 - Article

C2 - 12500307

AN - SCOPUS:0037413906

VL - 54

SP - 313

EP - 325

JO - Developmental Neurobiology

JF - Developmental Neurobiology

SN - 1932-8451

IS - 2

ER -