Related Experiment Video

Updated: Dec 27, 2025

Characterization of Thymic Settling Progenitors in the Mouse Embryo Using In Vivo and In Vitro Assays
08:56

Characterization of Thymic Settling Progenitors in the Mouse Embryo Using In Vivo and In Vitro Assays

Published on: June 9, 2015

8.6K

PAX1 is essential for development and function of the human thymus

Yasuhiro Yamazaki1, Raul Urrutia2, Luis M Franco3

  • 1Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, MD 20892, USA.

Science Immunology
|March 1, 2020
PubMed

We investigated the molecular and cellular basis of severe combined immunodeficiency (SCID) in six patients with otofaciocervical syndrome type 2 who failed to attain T cell reconstitution after allogeneic hematopoietic stem cell transplantation, despite successful engraftment in three of them. We identified rare biallelic PAX1 rare variants in all patients. We demonstrated that these mutant PAX1 proteins have an altered conformation and flexibility of the paired box domain and reduced transcriptional activity. We generated patient-derived induced pluripotent stem cells and differentiated them into thymic epithelial progenitor cells and found that they have an altered transcriptional profile, including for genes involved in the development of the thymus and other tissues derived from pharyngeal pouches. These results identify biallelic, loss-of-function PAX1 mutations as the cause of a syndromic form of SCID due to altered thymus development.

More Related Videos

Two-step Approach to Explore Early- and Late-stages of Organ Formation in the Avian Model: The Thymus and Parathyroid Glands Organogenesis Paradigm13:43

Two-step Approach to Explore Early- and Late-stages of Organ Formation in the Avian Model: The Thymus and Parathyroid Glands Organogenesis Paradigm

Published on: June 17, 2018

7.8K
Author Spotlight: Advancing Thymic Epithelial Cells and T-Cell Research with Human Thymic Organoids03:31

Author Spotlight: Advancing Thymic Epithelial Cells and T-Cell Research with Human Thymic Organoids

Published on: October 4, 2024

2.2K

Related Concept Videos

Primary Lymphoid Organs01:16

Primary Lymphoid Organs

Primary lymphoid organs are pivotal in the formation, development, and maturation of lymphocytes, the white blood cells that serve as the backbone of our immune system. This crucial function underscores their fundamental role in maintaining our overall health and immunity. The two primary lymphoid organs of prime importance are the red bone marrow and the thymus.
The red bone marrow is a soft, spongy tissue nestled in the interior of long bones such as the humerus and femur. It is the site...
14.4K
Development of the Lymphatic System01:15

Development of the Lymphatic System

The development of lymphatic tissues and vessels in embryonic life begins around the fifth week. These structures originate from the mesoderm layer, with lymph sacs emerging from developing veins.
The first lymph sacs to form are the paired jugular lymph sacs located at the junction of the internal jugular and subclavian veins. From these sacs, lymphatic capillary plexuses extend to the thorax, upper limbs, neck, and head, eventually forming lymphatic vessels. Each jugular lymph sac maintains a...
1.8K
Pleiotropy01:33

Pleiotropy

Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
43.0K
Functions of Thyroid Hormones01:18

Functions of Thyroid Hormones

The thyroid hormone (TH) plays a pivotal role in the intricate orchestration of physiological processes, exerting profound effects on development, metabolism, and homeostasis throughout different life stages.
TH is indispensable for the normal development and maturation of the skeletal, muscular, and nervous systems during fetal and childhood growth. It facilitates bone mineral turnover and regulates protein synthesis in developing tissues, contributing significantly to overall growth and...
4.7K
General Transcription Factors01:30

General Transcription Factors

Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
6.6K
Development of Immunocompetence01:22

Development of Immunocompetence

The initiation of cell-mediated immunity can be observed as early as the third month of fetal growth, with active antibody-mediated immunity following approximately one month later.
The initial cells that migrate from the fetal thymus settle within the skin and epithelial tissues lining the mouth, digestive tract, and in females, the uterus and vagina. These cells, including skin-based dendritic cells, serve as antigen-presenting cells, playing a key role in T cell activation.
Subsequent T...
686