Abstract
BackgroundThe development of neural circuits within the embryonic cerebral cortex relies on the timely production of neurons, their positioning within the embryonic cerebral cortex as well as their terminal differentiation and dendritic spine connectivity. The RhoA GTPases Rnd2 and Rnd3 are important for neurogenesis and cell migration within the embryonic cortex (Nat Commun 4:1635, 2013), and we recently identified the BTB/POZ domain-containing Adaptor for Cul3-mediated RhoA Degradation family member Bacurd2 (also known as Tnfaip1) as an interacting partner to Rnd2 for the migration of embryonic mouse cortical neurons (Neural Dev 10:9, 2015).FindingsWe have extended this work and report that Bacurd1/Kctd13 and Bacurd2/Tnfaip1 are interacting partners to Rnd2 and Rnd3 in vitro. Given that these genes are expressed during cortical development, we performed a series of in utero electroporation studies in mice and found that disruptions to Bacurd1/Kctd13 or Bacurd2/Tnfaip1 expression impair the long-term positioning of E14.5-born cortical neurons within the postnatal (P17) mouse cerebral cortex. We also find that forced expression of Bacurd1/Kctd13 and Bacurd2/Tnfaip1 alters the branching and dendritic spine properties of layer II/III projection neurons.ConclusionsWe identify Bacurd1/Kctd13 and Bacurd2/Tnfaip1 as interacting partners to Rnd proteins which influence the development of cortical neurons. Their neurodevelopmental functions are likely to be relevant to human brain development and disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s13064-016-0062-1) contains supplementary material, which is available to authorized users.
Highlights
During development, newborn neurons undergo directional cell migration to position themselves appropriately within the embryonic cerebral cortex before establishing their branching characteristics and establishing dendritic spine connections
We identify Bacurd1/Kctd13 and Bacurd2/Tnfaip1 as interacting partners to Rnd proteins which influence the development of cortical neurons
BACURD1/KCTD13 and BACURD2/TNFAIP1 are expressed during mammalian cerebral cortex development in mice and humans (Additional file 1: Figure S1C-D; as well as [8, 15,16,17]) and we previously reported that forced expression of Bacurd2/Tnfaip1 impaired cell migration within the murine embryonic cortex but not their early neuronal differentiation, as determined by staining for βIII-tubulin [8]
Summary
Newborn neurons undergo directional cell migration to position themselves appropriately within the embryonic cerebral cortex before establishing their branching characteristics and establishing dendritic spine connections (reviewed in [1, 2]). E (See figure on previous page.) Fig. 1 Bacurd1/Kctd and Bacurd2/Tnfaip are interacting partners to Rnd2/3, and their forced expression impairs the long-term positioning of E14.5-born cortical projection neurons. We report that Bacurd1/ Kctd and Bacurd2/Tnfaip are interacting partners to Rnd and Rnd, and our functional studies demonstrate that alterations to Bacurd expression disrupt the development of neurons within the mouse cerebral cortex. The RhoA GTPases Rnd and Rnd are important for neurogenesis and cell migration within the embryonic cortex (Nat Commun 4:1635, 2013), and we recently identified the BTB/ POZ domain-containing Adaptor for Cul3-mediated RhoA Degradation family member Bacurd ( known as Tnfaip1) as an interacting partner to Rnd for the migration of embryonic mouse cortical neurons (Neural Dev 10:9, 2015)
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