Mammalian-specific sequences in pou3f2 contribute to maternal behavior

Area of Science:

• Evolutionary biology
• Neuroscience
• Genetics

Background:

• Orthologs are genes in different species that diverged from a common ancestral gene.
• Mammalian maternal behavior, such as pup retrieval, is a complex trait crucial for offspring survival.
• The transcription factor POU3F2 plays a role in mammalian development and behavior.

Purpose of the Study:

• To investigate the role of homopolymeric amino acid repeats in the transcription factor POU3F2 in mammalian maternal behavior.
• To determine the impact of POU3F2 orthologs lacking these repeats on pup retrieval and offspring survival.
• To explore the relationship between POU3F2, monoamine neurotransmitters, and maternal care.

Main Methods:

• Generation of nonmammalized mice by replacing the mouse Pou3f2 with its Xenopus ortholog lacking homopolymeric repeats.
• Generation of knock-in mice with mammalian POU3F2 but lacking all homopolymeric amino acid repeats.
• Quantitative immunohistochemical analysis of dopamine and serotonin synthesis enzymes in brain structures.
• Behavioral observation of pup retrieval in the modified mouse models.

Main Results:

• Nonmammalized mice exhibited a remarkable deterioration of pup retrieval behavior.
• Most pups born to nonmammalized mice died shortly after birth, dependent on dam genotype.
• Reduced levels of key enzymes for dopamine and serotonin synthesis were observed in the brains of modified mice.
• Knock-in mice lacking POU3F2 homopolymeric repeats showed similar behavioral and neurochemical deficits.

Conclusions:

• Homopolymeric amino acid repeats in POU3F2 are critical for normal mammalian pup retrieval behavior.
• The evolutionary acquisition of these repeats is strongly linked to maintaining adequate monoamine neurotransmitter levels.
• These findings elucidate a molecular mechanism connecting gene evolution, neurochemistry, and a fundamental mammalian maternal behavior.