Prdm8 regulates the morphological transition at multipolar phase during neocortical development.

Here, we found that the PR domain protein Prdm8 serves as a key regulator of the length of the multipolar phase by controlling the timing of morphological transition. We used a mouse line with expression of Prdm8-mVenus reporter and found that Prdm8 is predominantly expressed in the middle and upper...

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Autores principales:	Mayuko Inoue, Takao Kuroda, Aya Honda, Mariko Komabayashi-Suzuki, Tae Komai, Yoichi Shinkai, Ken-ichi Mizutani
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1d90a49a62f847ca8b6fbf57d8cfe8dd
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spelling	oai:doaj.org-article:1d90a49a62f847ca8b6fbf57d8cfe8dd2021-11-18T08:35:11ZPrdm8 regulates the morphological transition at multipolar phase during neocortical development.1932-620310.1371/journal.pone.0086356https://doaj.org/article/1d90a49a62f847ca8b6fbf57d8cfe8dd2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24489718/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Here, we found that the PR domain protein Prdm8 serves as a key regulator of the length of the multipolar phase by controlling the timing of morphological transition. We used a mouse line with expression of Prdm8-mVenus reporter and found that Prdm8 is predominantly expressed in the middle and upper intermediate zone during both the late and terminal multipolar phases. Prdm8 expression was almost coincident with Unc5D expression, a marker for the late multipolar phase, although the expression of Unc5D was found to be gradually down-regulated to the point at which mVenus expression was gradually up-regulated. This expression pattern suggests the possible involvement of Prdm8 in the control of the late and terminal multipolar phases, which controls the timing for morphological transition. To test this hypothesis, we performed gain- and loss-of-function analysis of neocortical development by using in utero electroporation. We found that the knockdown of Prdm8 results in premature change from multipolar to bipolar morphology, whereas the overexpression of Prdm8 maintained the multipolar morphology. Additionally, the postnatal analysis showed that the Prdm8 knockdown stimulated the number of early born neurons, and differentiated neurons located more deeply in the neocortex, however, majority of those cells could not acquire molecular features consistent with laminar location. Furthermore, we found the candidate genes that were predominantly utilized in both the late and terminal multipolar phases, and these candidate genes included those encoding for guidance molecules. In addition, we also found that the expression level of these guidance molecules was inhibited by the introduction of the Prdm8 expression vector. These results indicate that the Prdm8-mediated regulation of morphological changes that normally occur during the late and terminal multipolar phases plays an important role in neocortical development.Mayuko InoueTakao KurodaAya HondaMariko Komabayashi-SuzukiTae KomaiYoichi ShinkaiKen-ichi MizutaniPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 1, p e86356 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mayuko Inoue Takao Kuroda Aya Honda Mariko Komabayashi-Suzuki Tae Komai Yoichi Shinkai Ken-ichi Mizutani Prdm8 regulates the morphological transition at multipolar phase during neocortical development.
description	Here, we found that the PR domain protein Prdm8 serves as a key regulator of the length of the multipolar phase by controlling the timing of morphological transition. We used a mouse line with expression of Prdm8-mVenus reporter and found that Prdm8 is predominantly expressed in the middle and upper intermediate zone during both the late and terminal multipolar phases. Prdm8 expression was almost coincident with Unc5D expression, a marker for the late multipolar phase, although the expression of Unc5D was found to be gradually down-regulated to the point at which mVenus expression was gradually up-regulated. This expression pattern suggests the possible involvement of Prdm8 in the control of the late and terminal multipolar phases, which controls the timing for morphological transition. To test this hypothesis, we performed gain- and loss-of-function analysis of neocortical development by using in utero electroporation. We found that the knockdown of Prdm8 results in premature change from multipolar to bipolar morphology, whereas the overexpression of Prdm8 maintained the multipolar morphology. Additionally, the postnatal analysis showed that the Prdm8 knockdown stimulated the number of early born neurons, and differentiated neurons located more deeply in the neocortex, however, majority of those cells could not acquire molecular features consistent with laminar location. Furthermore, we found the candidate genes that were predominantly utilized in both the late and terminal multipolar phases, and these candidate genes included those encoding for guidance molecules. In addition, we also found that the expression level of these guidance molecules was inhibited by the introduction of the Prdm8 expression vector. These results indicate that the Prdm8-mediated regulation of morphological changes that normally occur during the late and terminal multipolar phases plays an important role in neocortical development.
format	article
author	Mayuko Inoue Takao Kuroda Aya Honda Mariko Komabayashi-Suzuki Tae Komai Yoichi Shinkai Ken-ichi Mizutani
author_facet	Mayuko Inoue Takao Kuroda Aya Honda Mariko Komabayashi-Suzuki Tae Komai Yoichi Shinkai Ken-ichi Mizutani
author_sort	Mayuko Inoue
title	Prdm8 regulates the morphological transition at multipolar phase during neocortical development.
title_short	Prdm8 regulates the morphological transition at multipolar phase during neocortical development.
title_full	Prdm8 regulates the morphological transition at multipolar phase during neocortical development.
title_fullStr	Prdm8 regulates the morphological transition at multipolar phase during neocortical development.
title_full_unstemmed	Prdm8 regulates the morphological transition at multipolar phase during neocortical development.
title_sort	prdm8 regulates the morphological transition at multipolar phase during neocortical development.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/1d90a49a62f847ca8b6fbf57d8cfe8dd
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Prdm8 regulates the morphological transition at multipolar phase during neocortical development.

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