Opposing Gradients of MicroRNA Expression Temporally Pattern Layer Formation in the Developing Neocortex

Shu, Pengcheng; Wu, Chao; Ruan, Xiangbin; Liu, Wei; Hou, Lin; Fu, Hongye; Wang, Ming; Liu, Chang; Zeng, Yi; Chen, Pan; Yin, Bin; Yuan, Jing; Qiang, Boqin; Peng, Xiaozhong; Zhong, Weimin

doi:10.1016/j.devcel.2019.04.017

Cited by 54 publications

(45 citation statements)

References 81 publications

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“…On the whole, Hmga2 transcripts are initially detected in most embryonic tissues and progressively become restricted to tissues that contain proliferative cells; Hmga2 expression is usually absent in adult tissues, except for the testis (where it seems required for meiosis of the spermatocytes), the lung, and the kidney [41][42][43]. Specific details of the expression of this gene or protein in the mouse have also been reported in studies on their roles in the developing neural tissue and other tissues [44][45][46][47][48][49][50][51]; we will deal with some of these in the following sections.…”

Section: Hmga2 Developmental Expressionmentioning

confidence: 86%

“…HMGA2 stands as a let-7 modulated effector of this switch in commitment/differentiation [254,256]. Interestingly, there is a timely aspect in this process that closely recalls the let-7/HMGA interplay taking place in neocortical histogenesis [44,51].…”

Section: Other Developmental Effects Of Hmgamentioning

confidence: 96%

“…The three miRNAs mir-9, mir-128, and let-7 are expressed according to dynamic temporal gradients that regulate layer formation in the developing neocortex. Expression of miR-9 and miR-128 was found to decrease, while that of let-7 was found to increase, during cortical development [51]. Hmga2 mRNA has let-7 target sites in its 3 UTR and therefore this miRNA prevents production of the HMGA2 protein in several cell types [28,[131][132][133].…”

Section: Hmga1 and Hmga2 In The Development Of The Cnsmentioning

confidence: 98%

“…It seems that the miRNAs do not have an instructive effect as to the cell fate per se, but only serve to address the cells to the appropriate layer that is being made at that time. In fact, let-7 overexpressing, or let-7 depleted cells, shift their laminar position towards an upper or deeper layer, respectively, but their final position and cell fate depends on the day when the NPCs where electroporated (that is, on their neurogenic state) [51].…”

Section: Hmga1 and Hmga2 In The Development Of The Cnsmentioning

confidence: 99%

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HMGA Genes and Proteins in Development and Evolution

Vignali

Marracci

2020

IJMS

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HMGA (high mobility group A) (HMGA1 and HMGA2) are small non-histone proteins that can bind DNA and modify chromatin state, thus modulating the accessibility of regulatory factors to the DNA and contributing to the overall panorama of gene expression tuning. In general, they are abundantly expressed during embryogenesis, but are downregulated in the adult differentiated tissues. In the present review, we summarize some aspects of their role during development, also dealing with relevant studies that have shed light on their functioning in cell biology and with emerging possible involvement of HMGA1 and HMGA2 in evolutionary biology.

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Section: Hmga2 Developmental Expressionmentioning

confidence: 86%

Section: Other Developmental Effects Of Hmgamentioning

confidence: 96%

Section: Hmga1 and Hmga2 In The Development Of The Cnsmentioning

confidence: 98%

Section: Hmga1 and Hmga2 In The Development Of The Cnsmentioning

confidence: 99%

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HMGA Genes and Proteins in Development and Evolution

Vignali

Marracci

2020

IJMS

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“…CSMN and CPN of layer V arise from a common progenitor pool, yet they acquire the highly divergent neuronal fates, projection identities, and circuit connectivities required for complex motor cortex output via the corticospinal tract, and expanded interhemispheric communication and integration via the corpus callosum, respectively. miRNAs have been implicated in early cortical development (28,29), in production of cortical progenitors (59-77), in cortical neuronal migration (56,66,76,(78)(79)(80)(81)(82)(83), and in the timing of neocortical layer production and progenitor competence (84). A mechanism of miRNAs controlling projection neuron fate specification in the nematode C. elegans has been demonstrated (85), however, no such mechanism yet has been demonstrated in mammals.…”

Section: Discussionmentioning

confidence: 99%

An evolutionarily acquired microRNA shapes development of mammalian cortical projections

Diaz

Siththanandan

et al. 2020

Preprint

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The corticospinal tract is unique to mammals and the corpus callosum is unique to placental mammals (eutherians). The emergence of these structures is thought to underpin the evolutionary acquisition of complex motor and cognitive skills. Corticospinal motor neurons (CSMN) and callosal projection neurons (CPN) are the archetypal projection neurons of the corticospinal tract and corpus callosum, respectively. Although a number of conserved transcriptional regulators of CSMN and CPN development have been identified in vertebrates, none are unique to mammals and most are co-expressed across multiple projection neuron subtypes. Here, we discover seventeen CSMN-enriched microRNAs (miRNAs), fifteen of which map to a single genomic cluster that is exclusive to eutherians. One of these, miR-409-3p, promotes CSMN subtype identity in part via repression of LMO4, a key transcriptional regulator of CPN development. In vivo, miR-409-3p is sufficient to convert deep-layer CPN into CSMN. This is the first demonstration of an evolutionarily acquired miRNA in eutherians that refines cortical projection neuron subtype development. Our findings implicate miRNAs in the eutherians’ increase in neuronal subtype and projection diversity, the anatomic underpinnings of their complex behavior.Significance StatementThe mammalian central nervous system contains unique projections from the cerebral cortex thought to underpin complex motor and cognitive skills, including the corticospinal tract and corpus callosum. The neurons giving rise to these projections - corticospinal and callosal projection neurons - develop from the same progenitors, but acquire strikingly different fates. The broad evolutionary conservation of known genes controlling cortical projection neuron fates raises the question of how the more narrowly conserved corticospinal and callosal projections evolved. We identify a microRNA cluster selectively expressed by corticospinal projection neurons and exclusive to placental mammals. One of these microRNAs promotes corticospinal fate via regulation of the callosal gene LMO4, suggesting a mechanism whereby microRNA regulation during development promotes evolution of neuronal diversity.

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R3HDM1 haploinsufficiency is associated with mild intellectual disability

Fukushi

Inaba

Katoh

et al. 2021

American J of Med Genetics Pt A

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R3HDM1 (R3H domain containing 1) is an uncharacterized RNA‐binding protein that is highly expressed in the human cerebral cortex. We report the first case of a 12‐year‐old Japanese male with haploinsufficiency of R3HDM1. He presented with mild intellectual disability (ID) and developmental delay. He had a pericentric inversion of 46,XY,inv(2)(p16.1q21.3)dn with breakpoints in intron 19 of R3HDM1 (2q21.3) and the intergenic region (2p16.1). The R3HDM1 levels in his lymphoblastoid cells were reduced to approximately half that of the healthy controls. However, the expression of MIR128‐1, in intron 18 of R3HDM1, was not affected via the pericentric inversion. Knockdown of R3HDM1 in mouse embryonic hippocampal neurons suppressed dendritic growth and branching. Notably, the Database of Genomic Variants reported the case of a healthy control with a 488‐kb deletion that included both R3HDM1 and MIR128‐1. miR‐128 has been reported to inhibit dendritic growth and branching in mouse brain neurons, which directly opposes the novel functions of R3HDM1. These findings suggest that deleting both R3HDM1 and MIR128‐1 alleviates the symptoms of the disease caused by loss‐of‐function mutations in R3HDM1 only. Thus, haploinsufficiency of R3HDM1 in the patient may be the cause of the mild ID due to the genetic imbalance between R3HDM1 and MIR128‐1.

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Opposing Gradients of MicroRNA Expression Temporally Pattern Layer Formation in the Developing Neocortex

Cited by 54 publications

References 81 publications

HMGA Genes and Proteins in Development and Evolution

HMGA Genes and Proteins in Development and Evolution

An evolutionarily acquired microRNA shapes development of mammalian cortical projections

R3HDM1 haploinsufficiency is associated with mild intellectual disability

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