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Int J Biol Sci 2023; 19(10):3226-3248. doi:10.7150/ijbs.78489 This issue Cite

Research Paper

Defective neurite elongation and branching in Nibp/Trappc9 deficient zebrafish and mice

Min Hu1#, Brittany Bodnar2#, Yonggang Zhang3#✉, Fangxin Xie3,6#, Fang Li2, Siying Li1, Jin Zhao1, Ruotong Zhao2, Naveen Gedupoori2, Yifan Mo2, Lanyi Lin2, Xue Li1, Wentong Meng1, Xiaofeng Yang2, Hong Wang2, Mary F. Barbe2, Shanthi Srinivasan5, John R. Bethea4, Xianming Mo1, Hong Xu1✉, Wenhui Hu1,2✉

1. Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
2. Center for Metabolic Disease Research, Department of Pathalogy and Laboratory Medicine, Temple University Lewis Katz School of Medicine, Philadelphia, PA, USA.
3. Center for Stem Cell Research and Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu 610052, China.
4. Department of Biology, Drexel University, Philadelphia, PA, USA.
5. Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
6. Department of Clinical Laboratory, Xi'an NO. 3 Hospital, Xi'an, Shaanxi, 710018, China.
# Contributed equally

✉ Corresponding authors: Wenhui Hu, Center for Metabolic Disease Research, Temple University Lewis Katz School of Medicine, 3500 N Broad Street, Philadelphia, PA 19140. Email: whuedu. Hong Xu, Laboratory of Stem Cell Biology, State Key Laborat More

Citation:
Hu M, Bodnar B, Zhang Y, Xie F, Li F, Li S, Zhao J, Zhao R, Gedupoori N, Mo Y, Lin L, Li X, Meng W, Yang X, Wang H, Barbe MF, Srinivasan S, Bethea JR, Mo X, Xu H, Hu W. Defective neurite elongation and branching in Nibp/Trappc9 deficient zebrafish and mice. Int J Biol Sci 2023; 19(10):3226-3248. doi:10.7150/ijbs.78489. https://www.ijbs.com/v19p3226.htm
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Abstract

Graphic abstract

Loss of function in transport protein particles (TRAPP) links a new set of emerging genetic disorders called “TRAPPopathies”. One such disorder is NIBP syndrome, characterized by microcephaly and intellectual disability, and caused by mutations of NIBP/TRAPPC9, a crucial and unique member of TRAPPII. To investigate the neural cellular/molecular mechanisms underlying microcephaly, we developed Nibp/Trappc9-deficient animal models using different techniques, including morpholino knockdown and CRISPR/Cas mutation in zebrafish and Cre/LoxP-mediated gene targeting in mice. Nibp/Trappc9 deficiency impaired the stability of the TRAPPII complex at actin filaments and microtubules of neurites and growth cones. This deficiency also impaired elongation and branching of neuronal dendrites and axons, without significant effects on neurite initiation or neural cell number/types in embryonic and adult brains. The positive correlation of TRAPPII stability and neurite elongation/branching suggests a potential role for TRAPPII in regulating neurite morphology. These results provide novel genetic/molecular evidence to define patients with a type of non-syndromic autosomal recessive intellectual disability and highlight the importance of developing therapeutic approaches targeting the TRAPPII complex to cure TRAPPopathies.

Citation styles

APA
Hu, M., Bodnar, B., Zhang, Y., Xie, F., Li, F., Li, S., Zhao, J., Zhao, R., Gedupoori, N., Mo, Y., Lin, L., Li, X., Meng, W., Yang, X., Wang, H., Barbe, M.F., Srinivasan, S., Bethea, J.R., Mo, X., Xu, H., Hu, W. (2023). Defective neurite elongation and branching in Nibp/Trappc9 deficient zebrafish and mice. International Journal of Biological Sciences, 19(10), 3226-3248. https://doi.org/10.7150/ijbs.78489.

ACS
Hu, M.; Bodnar, B.; Zhang, Y.; Xie, F.; Li, F.; Li, S.; Zhao, J.; Zhao, R.; Gedupoori, N.; Mo, Y.; Lin, L.; Li, X.; Meng, W.; Yang, X.; Wang, H.; Barbe, M.F.; Srinivasan, S.; Bethea, J.R.; Mo, X.; Xu, H.; Hu, W. Defective neurite elongation and branching in Nibp/Trappc9 deficient zebrafish and mice. Int. J. Biol. Sci. 2023, 19 (10), 3226-3248. DOI: 10.7150/ijbs.78489.

NLM
Hu M, Bodnar B, Zhang Y, Xie F, Li F, Li S, Zhao J, Zhao R, Gedupoori N, Mo Y, Lin L, Li X, Meng W, Yang X, Wang H, Barbe MF, Srinivasan S, Bethea JR, Mo X, Xu H, Hu W. Defective neurite elongation and branching in Nibp/Trappc9 deficient zebrafish and mice. Int J Biol Sci 2023; 19(10):3226-3248. doi:10.7150/ijbs.78489. https://www.ijbs.com/v19p3226.htm

CSE
Hu M, Bodnar B, Zhang Y, Xie F, Li F, Li S, Zhao J, Zhao R, Gedupoori N, Mo Y, Lin L, Li X, Meng W, Yang X, Wang H, Barbe MF, Srinivasan S, Bethea JR, Mo X, Xu H, Hu W. 2023. Defective neurite elongation and branching in Nibp/Trappc9 deficient zebrafish and mice. Int J Biol Sci. 19(10):3226-3248.

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