Developmental Disorders

Developmental disorders (DD) are extremely heterogeneous in pathology, covering a variety of neurological disorders such as autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and fragile X syndrome (FXS). Approximately 2-5% of children are born with severe congenital malformations and/or exhibit severe neurodevelopmental disorders during childhood.

Causes of Developmental Disorders

Many developmental disorders are caused by heterozygous mutations in general regulators governing cell function. For example, Treacher Collins syndrome (TCS), caused by heterozygous mutations in Pol I cofactor TCOF1 or subunits POLR1D and POLR1C. The craniofacial abnormalities of TCS are mainly caused by the decreased distribution of cranial neural crest cells (cNCCs) in the first and second pharyngeal arches. By exploring the molecular functions of DDX21, we found that the activation of P53 and the loss of DDX21 in chromatin can lead to the apoptosis of a group of cNCCs when nuclear dysfunction or ribosomal DNA (rDNA) damage, which further aggravates the abnormality of TCS. In addition, RAS-related C3 botulinum toxin substrate 1 (RAC1) is a widely studied Rho GTPase. As a core participant in neurodevelopment, it regulates many cell functions.

Fig.1 Model explaining cNCC-type selective effects of nucleolar dysfunction and rDNA damage in TCS. (Calo, 2018)

Potential Targets for Developmental Disorders

Src homology 2 (SH2)-containing protein tyrosine phosphatase 2 (SHP2), encoded by PTPN11, regulates cell proliferation, differentiation, apoptosis, and survival through various signaling pathways. The mutation and abnormal expression of SHP2 are related to human developmental disorders, leukemia, and several solid tumors, it may be an effective target for drugs to treat DDs in vivo.

Fig.2 Role of SHP2 in activation of several signaling pathways. (Shen, 2020)

Treatment of Developmental Disorders

At present, there is no effective drug treatment in the field of developmental disorders, most of them use behavioral therapy and psychotherapy to reduce the complications of DD. In the latest research, patients with developmental disorders for 6 months or more, has oral lipopolysaccharide derived from Pantoea agglomerans bacteria (LPSp), and the behavior, verbal ability, and communication disabilities associated with ASD/ADHD were improved in all patients. Thus, LPSp may represent a new treatment option in the area of DD.

Creative Biolabs has advanced experimental technology and experience in neurodevelopmental research. We can provide intermediate markers related to developmental disorders, as well as a complete set of procedures for research on experimental animals and subsequent detection and analysis. If you need any customized services or products, please feel free to contact us.

References

1. Calo, E.; et al. Tissue-selective effects of nucleolar stress and rDNA damage in developmental disorders. Nature. 2018, 554(7690): 112-117.
2. Shen, D.; et al. Therapeutic potential of targeting SHP2 in human developmental disorders and cancers. European journal of medicinal chemistry. 2020, 190: 112117.