Nap1 regulated cytoskeletal dynamics during cortical neuronal development

Appropriate neuronal positioning and differentiation in the developing cerebral cortex requires dynamic regulation of neuronal cytoskeleton. Although the significance of cytoskeletal dynamics during the neuronal proliferation and migration in cerebral cortex is well established, the cytoskeletal regulators that choreograph the change in the neuronal cytoskeletal machinery from one that promotes oriented motility to one that facilitates stable laminar positioning and elaboration of axons and dendrites at the appropriate locations in the cerebral cortex remains unknown. We found that Nck associated protein 1 (Nap1), an adaptor protein that is thought to modulate actin nucleation, is selectively expressed in the cortical plate region of the developing cortex, where neurons terminate their migration and initiate their laminar specific differentiation. Inhibition of Nap1 disrupts neuronal differentiation. Premature expression of Nap1 in migrating neurons retards their migration and promotes their layer specific, post migratory differentiation. Nap1 mutant mice in which the function of the Nap1 gene has been disrupted by insertional mutagenesis display profound neural tube formation and neuronal differentiation defects. Nap1 mutation disrupts lamellipodial formation and the ability to localize key actin cytoskeletal regulators such as WAVE1 to the protrusive edges of neurons where they are needed to elaborate process outgrowth. Together, these studies suggest that Nap1 may play an essential role in triggering the neuronal cytoskeletal changes underlying the post?migratory differentiation of cortical neurons, a critical step in functional wiring of the cerebral cortex

Constructing a comprehensive scope of Allied occupation resources

Joint presentation at the Committee on Japanese Materials of the Council of East Asia Libraries annual conference held in Washington D.C. on March 22, 2019. Yukako Tatsumi presented about the Prange collections at the University of Maryland Libraries, College Park, and Keiko Yokota-Carter presented on the Alfred Rodman Hussey Collection at the University of Michigan. Tokiko Yamamoto Bazzell presented about the Kaizawa collection at the University of Hawaii Library. Link: Tatsumi and Yokota-Carter https://www.eastasianlib.org/newsite/wp-content/uploads/2018/09/P3_TatsumiCarter_CJM2018_2.pdf Bazsell https://www.eastasianlib.org/newsite/wp-content/uploads/2018/09/P4_Bazzell_CJM2018_1.pdf 2018 CJM program is found https://www.eastasianlib.org/newsite/meetings/past-meetings/ceal2018/#cjm-programhttps://deepblue.lib.umich.edu/bitstream/2027.42/148157/1/2018 CEAL CJM No. 2 Michigan included.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148157/2/2018 CEAL CJM No. 1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148157/6/license_rdf17Description of 2018 CEAL CJM No. 2 Michigan included.pdf : Presentaton file posted with the approval by co-presenters Yukako Tatsumi and Tokiko Y. BazzellDescription of 2018 CEAL CJM No. 1.pdf : Presentation file posted by approval by the co-presenters; Yukako Tatsumi and Tokiko Y. Bazzel

Nap1-Regulated Neuronal Cytoskeletal Dynamics Is Essential for the Final Differentiation of Neurons in Cerebral Cortex

SummaryThe cytoskeletal regulators that mediate the change in the neuronal cytoskeletal machinery from one that promotes oriented motility to one that facilitates differentiation at the appropriate locations in the developing neocortex remain unknown. We found that Nck-associated protein 1 (Nap1), an adaptor protein thought to modulate actin nucleation, is selectively expressed in the developing cortical plate, where neurons terminate their migration and initiate laminar-specific differentiation. Loss of Nap1 function disrupts neuronal differentiation. Premature expression of Nap1 in migrating neurons retards migration and promotes postmigratory differentiation. Nap1 gene mutation in mice leads to neural tube and neuronal differentiation defects. Disruption of Nap1 retards the ability to localize key actin cytoskeletal regulators such as WAVE1 to the protrusive edges where they are needed to elaborate process outgrowth. Thus, Nap1 plays an essential role in facilitating neuronal cytoskeletal changes underlying the postmigratory differentiation of cortical neurons, a critical step in functional wiring of the cortex

Radial Glial Dependent and Independent Dynamics of Interneuronal Migration in the Developing Cerebral Cortex

Interneurons originating from the ganglionic eminence migrate tangentially into the developing cerebral wall as they navigate to their distinct positions in the cerebral cortex. Compromised connectivity and differentiation of interneurons are thought to be an underlying cause in the emergence of neurodevelopmental disorders such as schizophrenia. Previously, it was suggested that tangential migration of interneurons occurs in a radial glia independent manner. Here, using simultaneous imaging of genetically defined populations of interneurons and radial glia, we demonstrate that dynamic interactions with radial glia can potentially influence the trajectory of interneuronal migration and thus the positioning of interneurons in cerebral cortex. Furthermore, there is extensive local interneuronal migration in tangential direction opposite to that of pallial orientation (i.e., in a medial to lateral direction from cortex to ganglionic eminence) all across the cerebral wall. This counter migration of interneurons may be essential to locally position interneurons once they invade the developing cerebral wall from the ganglionic eminence. Together, these observations suggest that interactions with radial glial scaffold and localized migration within the expanding cerebral wall may play essential roles in the guidance and placement of interneurons in the developing cerebral cortex

3 1 integrin modulates neuronal migration and placement during early stages of cerebral cortical development

We show that alpha3 integrin mutation disrupts distinct aspects of neuronal migration and placement in the cerebral cortex. The preplate develops normally in alpha3 integrin mutant mice. However, time lapse imaging of migrating neurons in embryonic cortical slices indicates retarded radial and tangential migration of neurons, but not ventricular zone-directed migration. Examination of the actin cytoskeleton of alpha3 integrin mutant cortical cells reveals aberrant actin cytoskeletal dynamics at the leading edges. Deficits are also evident in the ability of developing neurons to probe their cellular environment with filopodial and lamellipodial activity. Calbindin or calretinin positive upper layer neurons as well as the deep layer neurons of alpha3 integrin mutant mice expressing EGFP were misplaced. These results suggest that alpha3beta1 integrin deficiency impairs distinct patterns of neuronal migration and placement through dysregulated actin dynamics and defective ability to search and respond to migration modulating cues in the developing cortex

Molecular typing of enterohemorrhagic Escherichia coli O157:H7 isolated in Okayama Prefecture using pulsed field gel electrophoresis and random amplification of polymorphic DNA.

Three outbreaks and many isolated cases of enterohemorrhagic Escherichia coli O157:H7 occurred in 1996 and 1997 in Okayama Prefecture, Japan. In an attempt to investigate the route of these infections, the strains isolated from the 3 outbreaks (total 33 strains) and 15 isolated cases (total 15 strains) were investigated using random amplification of polymorphic DNA (RAPD) and pulsed-field gel electrophoresis (PFGE). In addition, 10 strains from an outbreak in Tojo Cho, Hiroshima Prefecture (June 1996), 2 strains from the particular types of meat in Kochi Prefecture, and 42 strains isolated from bovine feces in a farm in Okayama Prefecture were also investigated in the same manner. PFGE was much more useful than RAPD for molecular typing of the clinical isolates, in that it allowed us to classify them into 10 PFGE groups. We noted that the strains differed according to the time and place of the outbreaks (or isolated cases). This indicates that O157:H7 infections in Okayama Prefecture were caused by different strains (although some cases were aggravated by the same strains as were found in other areas). The isolates from bovine feces were classified into 5 groups by PFGE profiles, but none of them were identical to those of the clinical isolates.</p

The Adenomatous Polyposis Coli Protein Is an Essential Regulator of Radial Glial Polarity and Construction of the Cerebral Cortex

Radial glia are highly polarized cells that serve as neuronal progenitors and as scaffolds for neuronal migration during construction of the cerebral cortex. How radial glial cells establish and maintain their morphological polarity is unknown. Using conditional gene targeting in mice, we demonstrate that Adenomatous Polyposis Coli (APC) serves an essential function in the maintenance of polarized radial glial scaffold during brain development. In the absence of APC, radial glial cells lose their polarity and responsiveness to the extracellular polarity maintenance cues, such as neuregulin-1. Elimination of APC further leads to marked instability of the radial glial microtubule cytoskeleton. The resultant changes in radial glial function and loss of APC in radial glial progeny lead to defective generation and migration of cortical neurons, severely disrupted cortical layer formation, and aberrant axonal tract development. Thus APC is an essential regulator of radial glial polarity and is critical for the construction of cerebral cortex in mammals

Arl13b-regulated cilia activities are essential for polarized radial glial scaffold formation

The construction of cerebral cortex begins with the formation of radial glia. Once formed, polarized radial glial cells divide either symmetrically or asymmetrically to balance appropriate production of progenitor cells and neurons. Upon birth, neurons use the processes of radial glia as scaffolding for oriented migration. Radial glia thus provide an instructive structural matrix to coordinate the generation and placement of distinct groups of cortical neurons in the developing cerebral cortex. Here we show that Arl13b, a cilia-specific small GTPase mutated in Joubert syndrome patients, is critical for the initial formation of the polarized radial progenitor scaffold. Through developmental stage-specific deletion of Arl13b in mouse cortical progenitors, we found that early neuroepithelial deletion of ciliary Arl13b leads to a reversal in the apical-basal polarity of radial progenitors and aberrant neuronal placement. Arl13b modulates ciliary signaling necessary for radial glial polarity. Our findings demonstrate that Arl13b signaling in primary cilia is important for the initial formation of a polarized radial glial scaffold and suggest that disruption of this process may contribute to aberrant neurodevelopment and brain abnormalities in Joubert syndrome-related ciliopathies