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Abrogation of MAP4K4 protein function causes congenital anomalies in humans and zebrafish

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Abrogation of MAP4K4 protein function causes congenital anomalies in humans and zebrafish. / Patterson, Victoria; Ullah, Farid; Bryant, Laura; Griffin, John N; Sidhu, Alpa; Saliganan, Sheila; Blaile, Mackenzie; Saenz, Margarita S; Smith, Rosemarie; Ellingwood, Sara; Grange, Dorothy K; Hu, Xuyun; Mireguli, Maimaiti; Luo, Yanfei; Shen, Yiping; Mulhern, Maureen; Zackai, Elaine; Ritter, Alyssa; Izumi, Kosaki; Hoefele, Julia; Wagner, Matias; Riedhammer, Korbinian M; Seitz, Barbara; Robin, Nathaniel H; Goodloe, Dana; Mignot, Cyril; Keren, Boris; Cox, Helen; Jarvis, Joanna; Hempel, Maja; Gibson, Cynthia Forster; Tran Mau-Them, Frederic; Vitobello, Antonio; Bruel, Ange-Line; Sorlin, Arthur; Mehta, Sarju; Raymond, F Lucy; Gilmore, Kelly; Powell, Bradford C; Weck, Karen; Li, Chumei; Vulto-van Silfhout, Anneke T; Giacomini, Thea; Mancardi, Maria Margherita; Accogli, Andrea; Salpietro, Vincenzo; Zara, Federico; Vora, Neeta L; Davis, Erica E; Burdine, Rebecca; Bhoj, Elizabeth.

In: SCI ADV, Vol. 9, No. 17, 28.04.2023, p. eade0631.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Patterson, V, Ullah, F, Bryant, L, Griffin, JN, Sidhu, A, Saliganan, S, Blaile, M, Saenz, MS, Smith, R, Ellingwood, S, Grange, DK, Hu, X, Mireguli, M, Luo, Y, Shen, Y, Mulhern, M, Zackai, E, Ritter, A, Izumi, K, Hoefele, J, Wagner, M, Riedhammer, KM, Seitz, B, Robin, NH, Goodloe, D, Mignot, C, Keren, B, Cox, H, Jarvis, J, Hempel, M, Gibson, CF, Tran Mau-Them, F, Vitobello, A, Bruel, A-L, Sorlin, A, Mehta, S, Raymond, FL, Gilmore, K, Powell, BC, Weck, K, Li, C, Vulto-van Silfhout, AT, Giacomini, T, Mancardi, MM, Accogli, A, Salpietro, V, Zara, F, Vora, NL, Davis, EE, Burdine, R & Bhoj, E 2023, 'Abrogation of MAP4K4 protein function causes congenital anomalies in humans and zebrafish', SCI ADV, vol. 9, no. 17, pp. eade0631. https://doi.org/10.1126/sciadv.ade0631

APA

Patterson, V., Ullah, F., Bryant, L., Griffin, J. N., Sidhu, A., Saliganan, S., Blaile, M., Saenz, M. S., Smith, R., Ellingwood, S., Grange, D. K., Hu, X., Mireguli, M., Luo, Y., Shen, Y., Mulhern, M., Zackai, E., Ritter, A., Izumi, K., ... Bhoj, E. (2023). Abrogation of MAP4K4 protein function causes congenital anomalies in humans and zebrafish. SCI ADV, 9(17), eade0631. https://doi.org/10.1126/sciadv.ade0631

Vancouver

Patterson V, Ullah F, Bryant L, Griffin JN, Sidhu A, Saliganan S et al. Abrogation of MAP4K4 protein function causes congenital anomalies in humans and zebrafish. SCI ADV. 2023 Apr 28;9(17):eade0631. https://doi.org/10.1126/sciadv.ade0631

Bibtex

@article{f3ef1ea1345a48828540e4d28566d700,
title = "Abrogation of MAP4K4 protein function causes congenital anomalies in humans and zebrafish",
abstract = "We report 21 families displaying neurodevelopmental differences and multiple congenital anomalies while bearing a series of rare variants in mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4). MAP4K4 has been implicated in many signaling pathways including c-Jun N-terminal and RAS kinases and is currently under investigation as a druggable target for multiple disorders. Using several zebrafish models, we demonstrate that these human variants are either loss-of-function or dominant-negative alleles and show that decreasing Map4k4 activity causes developmental defects. Furthermore, MAP4K4 can restrain hyperactive RAS signaling in early embryonic stages. Together, our data demonstrate that MAP4K4 negatively regulates RAS signaling in the early embryo and that variants identified in affected humans abrogate its function, establishing MAP4K4 as a causal locus for individuals with syndromic neurodevelopmental differences.",
keywords = "Animals, Humans, Zebrafish, Signal Transduction, Protein Serine-Threonine Kinases, Intracellular Signaling Peptides and Proteins",
author = "Victoria Patterson and Farid Ullah and Laura Bryant and Griffin, {John N} and Alpa Sidhu and Sheila Saliganan and Mackenzie Blaile and Saenz, {Margarita S} and Rosemarie Smith and Sara Ellingwood and Grange, {Dorothy K} and Xuyun Hu and Maimaiti Mireguli and Yanfei Luo and Yiping Shen and Maureen Mulhern and Elaine Zackai and Alyssa Ritter and Kosaki Izumi and Julia Hoefele and Matias Wagner and Riedhammer, {Korbinian M} and Barbara Seitz and Robin, {Nathaniel H} and Dana Goodloe and Cyril Mignot and Boris Keren and Helen Cox and Joanna Jarvis and Maja Hempel and Gibson, {Cynthia Forster} and {Tran Mau-Them}, Frederic and Antonio Vitobello and Ange-Line Bruel and Arthur Sorlin and Sarju Mehta and Raymond, {F Lucy} and Kelly Gilmore and Powell, {Bradford C} and Karen Weck and Chumei Li and {Vulto-van Silfhout}, {Anneke T} and Thea Giacomini and Mancardi, {Maria Margherita} and Andrea Accogli and Vincenzo Salpietro and Federico Zara and Vora, {Neeta L} and Davis, {Erica E} and Rebecca Burdine and Elizabeth Bhoj",
year = "2023",
month = apr,
day = "28",
doi = "10.1126/sciadv.ade0631",
language = "English",
volume = "9",
pages = "eade0631",
journal = "SCI ADV",
issn = "2375-2548",
publisher = "American Association for the Advancement of Science",
number = "17",

}

RIS

TY - JOUR

T1 - Abrogation of MAP4K4 protein function causes congenital anomalies in humans and zebrafish

AU - Patterson, Victoria

AU - Ullah, Farid

AU - Bryant, Laura

AU - Griffin, John N

AU - Sidhu, Alpa

AU - Saliganan, Sheila

AU - Blaile, Mackenzie

AU - Saenz, Margarita S

AU - Smith, Rosemarie

AU - Ellingwood, Sara

AU - Grange, Dorothy K

AU - Hu, Xuyun

AU - Mireguli, Maimaiti

AU - Luo, Yanfei

AU - Shen, Yiping

AU - Mulhern, Maureen

AU - Zackai, Elaine

AU - Ritter, Alyssa

AU - Izumi, Kosaki

AU - Hoefele, Julia

AU - Wagner, Matias

AU - Riedhammer, Korbinian M

AU - Seitz, Barbara

AU - Robin, Nathaniel H

AU - Goodloe, Dana

AU - Mignot, Cyril

AU - Keren, Boris

AU - Cox, Helen

AU - Jarvis, Joanna

AU - Hempel, Maja

AU - Gibson, Cynthia Forster

AU - Tran Mau-Them, Frederic

AU - Vitobello, Antonio

AU - Bruel, Ange-Line

AU - Sorlin, Arthur

AU - Mehta, Sarju

AU - Raymond, F Lucy

AU - Gilmore, Kelly

AU - Powell, Bradford C

AU - Weck, Karen

AU - Li, Chumei

AU - Vulto-van Silfhout, Anneke T

AU - Giacomini, Thea

AU - Mancardi, Maria Margherita

AU - Accogli, Andrea

AU - Salpietro, Vincenzo

AU - Zara, Federico

AU - Vora, Neeta L

AU - Davis, Erica E

AU - Burdine, Rebecca

AU - Bhoj, Elizabeth

PY - 2023/4/28

Y1 - 2023/4/28

N2 - We report 21 families displaying neurodevelopmental differences and multiple congenital anomalies while bearing a series of rare variants in mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4). MAP4K4 has been implicated in many signaling pathways including c-Jun N-terminal and RAS kinases and is currently under investigation as a druggable target for multiple disorders. Using several zebrafish models, we demonstrate that these human variants are either loss-of-function or dominant-negative alleles and show that decreasing Map4k4 activity causes developmental defects. Furthermore, MAP4K4 can restrain hyperactive RAS signaling in early embryonic stages. Together, our data demonstrate that MAP4K4 negatively regulates RAS signaling in the early embryo and that variants identified in affected humans abrogate its function, establishing MAP4K4 as a causal locus for individuals with syndromic neurodevelopmental differences.

AB - We report 21 families displaying neurodevelopmental differences and multiple congenital anomalies while bearing a series of rare variants in mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4). MAP4K4 has been implicated in many signaling pathways including c-Jun N-terminal and RAS kinases and is currently under investigation as a druggable target for multiple disorders. Using several zebrafish models, we demonstrate that these human variants are either loss-of-function or dominant-negative alleles and show that decreasing Map4k4 activity causes developmental defects. Furthermore, MAP4K4 can restrain hyperactive RAS signaling in early embryonic stages. Together, our data demonstrate that MAP4K4 negatively regulates RAS signaling in the early embryo and that variants identified in affected humans abrogate its function, establishing MAP4K4 as a causal locus for individuals with syndromic neurodevelopmental differences.

KW - Animals

KW - Humans

KW - Zebrafish

KW - Signal Transduction

KW - Protein Serine-Threonine Kinases

KW - Intracellular Signaling Peptides and Proteins

U2 - 10.1126/sciadv.ade0631

DO - 10.1126/sciadv.ade0631

M3 - SCORING: Journal article

C2 - 37126546

VL - 9

SP - eade0631

JO - SCI ADV

JF - SCI ADV

SN - 2375-2548

IS - 17

ER -