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Hippocampus is a critical component of the central nervous system. SRSF10 is expressed in central nervous system and plays important roles in maintaining normal brain functions. However, its role in hippocampus development is unknown. In this study, using SRSF10 conditional knock-out mice in neural progenitor cells (NPCs), we found that dysfunction of SRSF10 leads to developmental defects in the dentate gyrus of hippocampus, which manifests as the reduced length and wider suprapyramidal blade and infrapyramidal blade.Furthermore, we proved that loss of SRSF10 in NPCs caused inhibition of the differentiation activity and the abnormal migration of NPCs and granule cells, resulting in reduced granule cells and more ectopic granule cells dispersed in the molecular layer and hilus. Finally, we found that the abnormal migration may be caused by the radial glia scaffold and the reduced DISC1 expression in NPCs. Together, our results indicate that SRSF10 is required for the cell migration and formation of dentate gyrus during the development of hippocampus.

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During early postnatal brain development, the formation of proper synaptic connections between neurons is crucial for the development of functional neural networks. Recent studies have established the involvement of protease-mediated modulations of extracellular components in both synapse formation and elimination. The secretory serine protease neuropsin (also known as kallikrein-8) cleaves a few transmembrane or extracellular matrix proteins in a neural activity-dependent manner and regulates neural plasticity. However, neuropsin-dependent proteolysis of extracellular components and the involvement of these components in mouse brain development are poorly understood. We have observed that during hippocampus development, expression of neuropsin and levels of full-length or cleaved fragments of the neuropsin substrate protein L1 cell adhesion molecule (L1CAM) positively correlate with synaptogenesis. Our subcellular fractionation studies show that the expression of neuropsin and its proteolytic activity on L1CAM are enriched at developing hippocampal synapses. Activation of neuropsin expression upregulates the transcription and cleavage of L1CAM. Furthermore, blocking of neuropsin activity, as well as knockdown of L1CAM expression, significantly downregulates in vitro hippocampal synaptogenesis. Taken together, these findings provide evidence for the involvement of neuropsin activity-dependent regulation of L1CAM expression and cleavage in hippocampal synaptogenesis.

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The hippocampus is a complex structure composed of distinct subfields. It has been central to understanding neural foundations of episodic memory. In the current cross-sectional study, using a large sample of 830, 3- to 21-year-olds from a unique, publicly available dataset we examined the following questions: (1) Is there elevated grey matter volume of the hippocampus and subfields in late compared to early development? (2) How does hippocampal volume compare with the rest of the cerebral cortex at different developmental stages? and (3) What is the relation between hippocampal volume and connectivity with episodic memory performance? We found hippocampal subfield volumes exhibited a nonlinear relation with age and showed a lag in volumetric change with age when compared to adjacent cortical regions (e.g., entorhinal cortex). We also observed a significant reduction in cortical volume across older cohorts, while hippocampal volume showed the opposite pattern. In addition to age-related differences in gray matter volume, dentate gyrus/cornu ammonis 3 volume was significantly related to episodic memory. We did not, however, find any associations with episodic memory performance and connectivity through the uncinate fasciculus, fornix, or cingulum. The results are discussed in the context of current research and theories of hippocampal development and its relation to episodic memory.

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Objective: To investigate the expressions of phosphorylated extracellular signal-regulated kinase (pERK) in the hippocampus of the mice of embryonic (E) 18 d and postnatal (P) 1, 3, 7, 14, 21 and 28 d, and to discuss its possible role during the hippocampus development of the mice. Methods: The hippocampus tissues of the mice of E 18 d, P 1 d, P 3 d, P 7 d, P 14 d, P 21 d and P 28 d were obtained. Each time point was used as observation group. Immunohistochemistry, Western blotting and image analysis technique were used to analyze the expression levels of pERK protein in hippocampus tissue at each time point. Results: The immunohistochemistry results revealed that pERK protein mainly expressed in the nucleus of the nerve cells in the granular layer of dentate gyrus and pyramidal layer of Ammon' s horn in hippocampus. In the mice of E 18 d, the expression of pERK in DG and CA regions of hippocampus were slightly stained and arranged sparsely, and the expression level was low; and the pERK was deeply stained and the expression levels of pERK were increased gradually with the development of the hippocampus from E 18d to P 7 d; compared with other six time points, the expression level of pERK of the mice of P 7 d was the highest (F=34. 537, P0.05). The Western blotting results showed that pERK expressed at each time point, from E18 d to P7 d, the expression levels of pERK were increased gradually; compared with other six time points, the expression level of pERK on P 7 d was the highest (F = 33.856, P0.05). Conclusion: The hippocampus development is increased significantly at the early stage of the mice (E18 - P 7 d), and the expression levels of pERK are increased gradually in the meanwhile; the expression level peaks on P 7 d, and then it is gradually decreased until a stable level. pERK may take part in the cell proliferation in the development of hippocampus of the mice.

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In human telencephalon at 8-12 postconceptional weeks, ribonucleic acid quantitative sequencing and immunohistochemistry revealed cortical chicken ovalbumin upstream promotor-transcription factor 1 (COUP-TFI) expression in a high ventro-posterior to low anterior gradient except for raised immunoreactivity in the anterior ventral pallium. Unlike in mouse, COUP-TFI and SP8 were extensively co-expressed in dorsal sensory neocortex and dorsal hippocampus whereas COUPTFI/COUPTFII co-expression defined ventral temporal cortex and ventral hippocampus. In the ganglionic eminences (GEs) COUP-TFI immunoreactivity demarcated the proliferative zones of caudal GE (CGE), dorsal medial GE (MGE), MGE/lateral GE (LGE) boundary, and ventral LGE whereas COUP-TFII was limited to ventral CGE and the MGE/LGE boundary. Co-labeling with gamma amino butyric acidergic interneuron markers revealed that COUP-TFI was expressed in subpopulations of either MGE-derived (SOX6+) or CGE-derived (calretinin+/SP8+) interneurons. COUP-TFII was mainly confined to CGE-derived interneurons. Twice as many GAD67+ cortical cells co-labeled for COUP-TFI than for COUP-TFII. A fifth of COUP-TFI cells also co-expressed COUP-TFII, and cells expressing either transcription factor followed posterior or anterio-lateral pathways into the cortex, therefore, a segregation of migration pathways according to COUP-TF expression as proposed in mouse was not observed. In cultures differentiated from isolated human cortical progenitors, many cells expressed either COUP-TF and 30% also co-expressed GABA, however no cells expressed NKX2.1. This suggests interneurons could be generated intracortically from progenitors expressing either COUP-TF.

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Objective To investigate the role of neuro-specific DNA repair gene Nbn in mouse hippocampus development by observing the morphological differences in Nbn-CNS-Del and Nbn-CNS-Ctr mice.Methods Serial sections and stereology were used to quantitatively analyze the development of mouse hippocampus on postnatal day 7,14 and 21.Results Compared with that of the control group,the hippocampus development of Nbn-CNS-Del mice lagged behind.In Nbn-CNS-Del mice,on day 21,the profile area of pyramidal layer of hippocampus and granular layer of dentate gyrus decreased(P