Absence of the RING domain in MID1 results in patterning defects in the developing human brain

Frank S, Gabassi E, Käseberg S, Bertin M, Zografidou L, Pfeiffer D, Brennenstuhl H, Falk S, Karow M, Schweiger S (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Book Volume: 7

Journal Issue: 4

DOI: 10.26508/lsa.202302288

Abstract

The X-linked form of Opitz BBB/G syndrome (OS) is a monogenic disorder in which symptoms are established early during embryonic development. OS is caused by pathogenic variants in the X-linked gene MID1 Disease-associated variants are distributed across the entire gene locus, except for the N-terminal really interesting new gene (RING) domain that encompasses the E3 ubiquitin ligase activity. By using genome-edited human induced pluripotent stem cell lines, we here show that absence of isoforms containing the RING domain of MID1 causes severe patterning defects in human brain organoids. We observed a prominent neurogenic deficit with a reduction in neural tissue and a concomitant increase in choroid plexus-like structures. Transcriptome analyses revealed a deregulation of patterning pathways very early on, even preceding neural induction. Notably, the observed phenotypes starkly contrast with those observed in MID1 full-knockout organoids, indicating the presence of a distinct mechanism that underlies the patterning defects. The severity and early onset of these phenotypes could potentially account for the absence of patients carrying pathogenic variants in exon 1 of the MID1 gene coding for the N-terminal RING domain.

Authors with CRIS profile

Involved external institutions

Universitätsmedizin der Johannes Gutenberg-Universität Mainz Germany (DE) Ruprecht-Karls-Universität Heidelberg Germany (DE)

How to cite

APA:

Frank, S., Gabassi, E., Käseberg, S., Bertin, M., Zografidou, L., Pfeiffer, D.,... Schweiger, S. (2024). Absence of the RING domain in MID1 results in patterning defects in the developing human brain. Life Science Alliance, 7(4). https://doi.org/10.26508/lsa.202302288

MLA:

Frank, Sarah, et al. "Absence of the RING domain in MID1 results in patterning defects in the developing human brain." Life Science Alliance 7.4 (2024).

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