Biology subjects

Nishinakamura, R.

Publications and source records attributed to Nishinakamura, R..

4 recordsLinked to original sources

bioRxiv2026

The unconventional kinesin Kif26a is required for the guidance of major axon tracts in the developing mouse brain

Kif26a and Kif26b encode a family of unconventional kinesins with emerging roles in neurodevelopment, and mutations in both genes have been implicated in a spectrum of neurodevelopmental disorders. The precise mechanisms by which the Kif26 family orchestrates mammalian brain development, however, remain unclear. In this study, we show that Kif26a and Kif26b are expressed in distinct regions of the developing mouse brain. Using a new allelic series in mice, we demonstrate that Kif26a is required for the guidance of multiple forebrain axon tracts. This requirement is direct and cell autonomous, as cell proliferation, survival, and cortical layering are unaffected in the Kif26a mutants. These guidance defects closely resemble those reported for the Fzd3-Celsr3-Dystroglycan pathway, suggesting that Kif26a may participate within this conserved signaling axis to steer growing axons.

neuroscience↗

bioRxiv2022

The zinc finger transcription factor Sall1 is required for the early developmental transition of microglia in mouse embryos

Microglia play many critical roles in neural development. Recent single-cell RNA-sequencing studies have found diversity of microglia both across different stages and within the same stage in the developing brain. However, how such diversity is controlled during development is poorly understood. In this study, we first found the expression of the macrophage mannose receptor CD206 in early-stage embryonic microglia on mouse brain sections. This expression showed a sharp decline between E12.5 and E13.5 across the central nervous system. We next tested the roles of the microglia-expressed zinc finger transcription factor SALL1 in this early transition of gene expression. By deleting Sall1 specifically in microglia, we found that many microglia continued to express CD206 when it is normally downregulated. In addition, the mutant microglia continued to show less ramified morphology in comparison with controls even into postnatal stages. Thus, SALL1 is required for early microglia to transition into a more mature status during development.

neuroscience↗

bioRxiv2019

Over-activation of BMP signaling in neural crest cells precipitates heart outflow tract septation

Establishment of separated pulmonary and systemic circulations in vertebrates relies on the key role of neural crest cells (NCC) for the septation of the embryonic cardiac outflow tract (OFT). Absence of NCCs induces OFT septation defects, analogous to a loss of Bone Morphogenetic Proteins (BMPs) activity, though it remains unclear how BMPs control cardiac NCC differentiation and behaviour. To address this question, we monitored cardiac NCC state upon gain in BMP signaling, caused by the deletion of Dullard, using 3D-imaging and single cell transcriptomics. Specific loss of Dullard in the NCC results in premature OFT septation, pulmonary artery obstruction and embryonic death. This is caused by uncontrolled NCC convergence towards the endocardium and asymmetrical myocardial differentiation, promoted by elevated levels of the guiding cue Sema3c and decreased levels in mesenchymal trait markers. Furthermore, we unraveled the molecular basis of the zipper-like OFT septation where graded Sema3c expression follow a gradient of BMP activation in NCC along the OFT length.

developmental biology↗

bioRxiv2017

Transcriptional control by Sall4 in blastocysts facilitates lineage commitment of inner cell mass cells

The enhancer-binding zinc finger transcription factor Sall4 is essential for early mammalian postimplantation development and plays important roles in lineage commitment of embryonic stem cells. Enhancer binding by Sall4 results in transcriptional activation of some genes, but repression of others. Exactly how cells in preimplantation stage embryos use this transcriptional modulatory activity of Sall4 during early developmental transitions has not been determined. Using single cell gene expression analyses we show that Sall4 is required to maintain the gene regulatory network in inner cell mass (ICM) cells prior to lineage commitment. Although Sall4 is not required for ICM cells to adopt a correct epiblast or primitive endoderm gene expression profile, in the absence of Sall4 early ICM cells commit to either lineage at reduced frequency. We propose a model whereby Sall4 activity sets the stage for efficient progression from the uncommitted ICM progenitor state by modulating the gene regulatory network in early ICM cells.

developmental biology↗