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Evolutionarily conserved developmental pathways



Neuron differentiation - Involvement of POU domain protein in the terminal differentiation of neurons

The function of POU homeodomain proteins is not limited to neurons, but the evolutionary proliferation of classes of POU domain proteins and their ubiquitous involvement in the terminal differentiation of neurons suggests an evolutionarily conserved function. Drosophila has proteins from three POU domain classes. PDM1 and PDM2 are class II type POU domain proteins. Drifter is a class III member, and IPOU is from class IV. All four are involved in neural differentiation. Both PDM1 and PDM2 are required for the normal development of the GMC-1 lineage and the two collaborate during the specification of GMC-1 identity. Drifter is associated with defects in ventral midline glial migration. Although IPOU is expressed in neurons, the role of IPOU in development is unknown.

In Xenopus, in the absence of mesoderm induction, XIPOU 2, a class III member, has the ability to induce a neuronal phenotype in uncommitted ectoderm. Xenopus XIPOU 2 is expressed initially in Spemann's organizer, and later, in discrete regions of the developing nervous system. Deletion of the murine Brn-2, another class III member, results in loss of endocrine hypothalamic nuclei and the posterior pituitary gland. Lack of Brn-2 does not affect initial hypothalamic developmental events, but instead results in a failure of differentiation to mature neurosecretory neurons.The class IV POU homeo box gene unc-86 specifies neuroblast and neural identities in the developing C. elegans nervous system. Restriction of Brn-3.0, a mammalian class IV protein, expressed in post-mitotic CNS neurons demonstrates that Brn-3.0 is not required for neurogenesis or patterning of the neuroepithelium in the CNS, but suggests a role in specification of mature neuronal phenotypes. Thus, unlike the proneural basic HLH transcription factors, POU homeodomain proteins appear not to be involved in the initial stages of neurogenesis, but is involved later in the determination of neural identity.

Drosophila                        Homologs in other species ----------                        ----------------------------PDM-1                             Mammals: Oct1, Oct2, and Oct11PDM-2                             Mammals: Oct1, Oct2, and Oct11          Drifter                           C. elegans: CEH6                                  Zebrafish: ZFPOU 1 and   ZP-50                                  Xenopus: XIPOU 1 and XIPOU 2                                  Mammals: Brn1, Brn2, Brn4, SCIP/Oct6                                                        I-POU                             C. elegans: UNC86                                  Mammals: Brn3.0, Brn3.1 and Brn 3.2

date revised: 25 Feb 97

Developmental Pathways conserved in Evolution

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